Oxidative stress and cardiovascular diseases

Clin J Am Soc Nad 11 10 — Streess sepiapterin Natural ways to boost energy levels deficiency in DOCA-salt hypertension. Weight loss and sports injuries mobile search Weight loss and sports injuries Article Navigation. C Redox modification of sodium—calcium exchange activity in cardiac czrdiovascular vesicles J Biol Chem cardivoascular Indeed, Prx has an important influence on myocardial tissue and the overexpression of Prdx1 in cardiomyocytes was recently proposed to confer protection against cardiac hypertrophy and heart failure in the presence of pressure overload [ 86 ]. Importantly, while ROS production was originally considered to incite harmful effects, and low levels of ROS are necessary for physiological processes, including cell proliferation, migration, differentiation, and cytoskeletal organization [ 17 ]. Circulation 92—

Oxidative stress and cardiovascular diseases -
The activation of parasympathetic nervous system may exert protective effects in cardiopulmonary diseases through cholinergic anti-inflammatory pathway by controlling innate immune responses To better understand the involvement of the parasympathetic in pulmonary diseases, Qiu et al.

demonstrated that donepezil, an oral cholinesterase inhibitor therapy, attenuates pulmonary vascular and right ventricular remodeling by enhancing parasympathetic activity in a monocrotaline-induced PAH rat model. Additionally, these authors demonstrated that donepezil mediated effects for reducing hyper-proliferation and apoptosis-resistant phenotype of pulmonary arterial smooth muscle cells in PAH by suppressing the activation of M2-macrophage immune cells.

Immune cells, including macrophages, express both adrenergic and nicotinic receptors that bind with neurotransmitters such as acetylcholine released by sympathetic and parasympathetic nerve endings in order to initiate immune-modulatory responses Both the sympathetic and parasympathetic nervous systems are influential in producing neuro-immune processes It is well-established that macrophages are effector cells during an innate immune response.

The innate immune response calls the adaptive immune response into play. Both immune systems work together to make antibodies that act independently against extracellular pathogens and toxins Although sometimes an overactive immune system can generate antibodies that are specific to self-molecules or tissues which are referred to as autoantibodies Formation of these autoantibodies has now been recognized as a key factor for the high prevalence of PAH patients 28 , In line with previously published data, Shu et al.

summarized the importance of the lung based cell specific immune response, the potential auto-antigens and the modulating role of local immunoglobulin in pathogenesis of PAH including the development of precise therapy in PAH patients.

Most intriguingly, recent studies have indicated that patients with common lung diseases, including chronic obstructive pulmonary disease COPD are more likely to develop pulmonary hypertension PH and other cardiovascular diseases 30 , To increase the understanding about COPD, Karnati et al.

summarized the role of oxidative stress in COPD and PH by describing a detailed description on the pathogenesis of pulmonary vascular remodeling. Next, published evidence indicates that COPD patients are at increased risk of suffering from various cardiovascular diseases including heart failure, ischemic heart, and hypertension 31 , Interestingly, about one third of patients with COPD are obese 32 , To better understand the role of obesity in vascular dysfunction, Zhou et al.

summarized the current understanding of the relationship between oxidative stress in obesity and vascular endothelial dysfunction. In this review, they described the possible risk factors of oxidative stress in obesity, and the impact of obesity-induced oxidative stress on adipose tissue function.

Additionally, their review highlights the crosstalk between adipose tissue and vasculature mediated by adipocytokines as well as the potential target mediating adipose tissue oxidative stress.

With the significant increase of understanding about obesity in scientific research, adipose tissue is now considered as a central metabolic organ in the regulation of whole-body energy homeostasis by lipid metabolism 34 , It has been well-characterized that excessive alcohol consumption, also known as binge drinking results in dysregulated lipid metabolism within adipose tissue To better understand this process, Seidel et al.

focussed their research work on the role of binge drinking on specific S-glutathionylation in the aorta, liver, and brain by using an ApoE deficient mouse model. Their findings reported that binge drinking led to aorta- and liver-specific regulation of the glutathionylation regulatory enzyme system, eliciting decreased glutaredoxin-1 and increased glutathione S-transferase.

Precisely, they suggested that the activation of aorta- and liver-based S-glutathionylation compromises aortic endothelial dysfunction and fatty liver, which might be a potential underlying mechanism of increased risk factor for cardiovascular diseases among binge drinkers.

Understanding the complexity of oxidative stress, Wang et al. summarized the mechanistic role of ROS on various intracellular signaling such as toll like receptor-4, nuclear factor kappa B cells, mitogen-activated protein kinase, CD26, heme oxygenase-1, transient receptor potential ion channels and L-type voltage-gated calcium channel in numerous diseases such as diabetes mellitus, hypertension, and ischemia-reperfusion injury.

In conclusion, the above-cited articles for this Research Topic indicate the current ideas and perspectives on the clinical impact from bench side research on the role of oxidative stress that plays in cardiovascular and pulmonary diseases. We believe that these articles provide a significant contribution of new ideas and advancements in the medical fields.

We are grateful to our all contributors for sharing their important work for this Research Topic. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Smolders VF, Zodda E, Quax PHA, Carini M, Barbera JA, Thomson TM, et al. Metabolic alterations in cardiopulmonary vascular dysfunction.

Front Mol Biosci. doi: PubMed Abstract CrossRef Full Text Google Scholar. Labaki WW, Han MK. Chronic respiratory diseases: a global view. Lancet Respir Med. Sack MN, Fyhrquist FY, Saijonmaa OJ, Fuster V, Kovacic JC. Basic biology of oxidative stress and the cardiovascular system: part 1 of a 3-part series.

J Am Coll Cardiol. Forman HJ, Zhang H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov. Tarafdar A, Pula G. The role of nadph oxidases and oxidative stress in neurodegenerative disorders. Int J Mol Sci. Wang K, Zhang T, Dong Q, Nice EC, Huang C, Wei Y.

Redox homeostasis: the linchpin in stem cell self-renewal and differentiation. Cell Death Dis. Snezhkina AV, Kudryavtseva AV, Kardymon OL, Savvateeva MV, Melnikova NV, Krasnov GS, et al. Ros generation and antioxidant defense systems in normal and malignant cells.

Oxid Med Cell Longev. Munzel T, Daiber A, Ullrich V, Mulsch A. K Antioxidant changes in hypertrophied and failing guinea pig hearts Am J Physiol Heart and Circ. F Singal P. K Role of oxidative stress in transition of hypertrophy to heart failure J Am Coll Cardiol 28 Hill M. K Antioxidant and oxidative stress changes during heart failure subsequent to myocardial infarction in rats Am J Pathol K Right and left myocardial antioxidant responses during heart failure subsequent to myocardial infarction Circulation 96 Khaper N Singal P.

K Effects of afterload reducing drugs on the pathogenesis of antioxidant changes and congestive heart failure in rats J Am Coll Cardiol 29 Packer L Protective role of vitamin E in biological systems Am J Clin Nutr 53 Axford-Gatley R.

A Wilson G. J Reduction of experimental myocardial infarct size by oral administration of alpha tocopherol Cardiovasc Res 25 89 Mickle D. D Myocardial salvage with trolox and ascorbic acid for an acute evolving infarction Ann Thorac Surg 47 Massey K.

D Burton K. P Alpha tocopherol attenuates myocardial membrane-related alterations resulting from ischemia and reperfusion Am J Physiol H H Klein H. H Pich S Lindert S et al. Combined treatment with vitamin E and C in experimental myocardial infarction in pigs Am Heart J Saraste A Pulkki K Kallajoki M et al.

Apoptosis in human acute myocardial infarction Circulation 95 Narula J Haider N Virmani R et al. Programmed myocyte death in end-stage heart failure N Engl J Med Olivetti G Abbi R Quaini F et al.

Apoptosis in the failing human heart N Engl J Med Gottlieb R. A Burleson K. O Kloner R. A Babior B. M Engler R. L Reperfusion injury induces apoptosis in rabbit cardiomyocytes J Clin Invest 94 Kajstura J Cheng W Reiss K et al.

Apoptotic and necrotic myocyte cell death are independent contributing variables of infarct size in rats Lab Invest 74 86 Teiger E Dam T. Apoptosis in pressure overload-induced heart hypertrophy in the rat J Clin Invest 97 Hockenbery D.

M Oltvai Z. N Yin X. L Korsmeyer S. J Bcl-2 functions in an antioxidant pathway to prevent apoptosis Cell 75 Buttke T. M Sandstrom P. A Oxidative stress as a mediator of apoptosis Immunol Today 15 7 Kumar D, Kirshenbaum L, Li T, Palace V, Singal PK. Apoptotic and necrotic cardiac cell death in adriamycin cardiomyopathy.

J Mol Cell Cardiol ; A, Forrest V. J Kang Y. E Robinson D. H Ramakrishnan N Oxidative stress-induced apoptosis prevented by trolox Free Radic Biol Med 16 Sandstrom P.

A Buttke T. M Autocrine production of extracellular catalase prevents apoptosis of the human CEM T-cell line in serum-free medium Proc Natl Acad Sci USA 90 Dimmeler S Haendeler J Galle J Zeiher A.

M Oxidized low-density lipoprotein induces apoptosis of human endothelial cells by activation of CPPlike proteases. A de Moissac D The bcl-2 gene product presents programmed cell death of ventricular myocytes Circulation 96 Weitz Z Birnbaum A.

J Sobotka P. A Zarling E. J Skosey J. L Elevated pentane levels during acute myocardial infarction Lancet Roberts M. D Young I. S Trouton T. G et al. Transient release of lipid peroxides after coronary artery balloon angioplasty Lancet Sobotka P.

A Brottman M. D Weitz Z et al. Elevated breath pentane in heart failure reduced by free radical scavenger Free Radic Biol Med 14 Diaz-Velez C. R Garcia-Castineiras S Mendoza-Ramos E Hernandez-Lopez E Increased malondialdehyde in peripheral blood of patients with congestive heart failure Am Heart J Charney RH, Levy DK, Kalman J, Buchholz E, et al.

Free radical activity increased with NYHA class in congestive heart failure. J Am Coll Cardiol ;, A, Suppl. Belch J. J Bridges A. B Scott N Chopra M Oxygen free radicals and congestive heart failure Br Heart J 65 McMurray J Mclay J Chopra M Bridges A Belch J.

F Evidence for enhanced free radical activity in chronic congestive heart failure secondary to coronary artery disease Am J Cardiol 65 McMurray J Chopra M Abdullah I Smith W. E Dargie H. J Evidence of oxidative stress in chronic heart failure in humans Eur Heart J 4 Cavarocchi N.

C England M. D O'Brien J. F et al. Superoxide generation during cardiopulmonary bypass: is there a role for vitamin E? J Surg Res 40 6 Scragg R Jackson R Holdaway I Woollard G Woollard D Changes in plasma vitamin E levels in the first 48 hrs after onset of acute myocardial infarction Am J Cardiol 64 Grech E Jack C.

I Bleasdale C Jackson M. J et al. Differential free radical activity after successful and unsuccessful thrombolytic reperfusion in acute myocardial infarction Coron Artery Dis 4 Stephens N.

G Parsons A Schofield P. M et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study CHAOS Lancet Rimm E. B Stampfer M. J Ascherio A et al. Vitamin E consumption and the risk of coronary disease in men N Engl J Med Stampfer M. J Hennekens C.

H Manson J. E et al. Vitamin E consumption and the risk of coronary disease in women N Engl J Med Herbaczynska-Cedro K Ktosiewicz-Wasek B Cedro K et al. Supplementation with vitamins C and E suppresses leukocyte oxygen free radical production in patients with myocardial infarction Eur Heart J 16 Singh R.

B Niaz M. A Rastogi S Usefulness of antioxidant vitamins in suspected acute myocardial infarction the Indian experiment of infarct survival — 3 Am J Cardiol 77 Chatelain E Boscoboinik D. O Bartoli G. Inhibition of smooth muscle cell proliferation and protein kinase C activity by tocopherols and tocotrienols Biochim Biophys Acta 83 Ozer N.

K Boscoboinik D Azzi A New roles of low density lipoproteins and vitamin E in the pathogenesis of atherosclerosis Biochem Mol Biol Int 35 Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.

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Journal Article. The role of oxidative stress in the genesis of heart disease. a a Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Tache Avenue, R, Winnipeg, MB R2H 2A6, Canada.

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Abstract Although researchers in radiation and cancer biology have known about the existence of free radicals and their potential role in pathobiology for several decades, cardiac biologists only began to take notice of these noxious species in the s.

Free radicals , Antioxidants , Heart failure. Open in new tab Download slide. Superoxide dismutase. An enzymatic function for erythrocuprein hemecuprein. Google Scholar PubMed. OpenURL Placeholder Text. Google Scholar Crossref. Search ADS. Time course of structure, function and metabolic changes due to an exogenous source of oxygen metabolites in rat heart.

Influence of oxygen radicals generated by xanthine oxidase in the isolated perfused rat heart. Potential oxidative pathways of catecholamines in the formation of lipid peroxides and genesis of heart disease. Disturbance of metabolism and cardiac function under the action of emotional painful stress and their prophylaxis.

Mediation of sarcoplasmic reticulum disruption in the ischemic myocardium: proposed mechanism by the interaction of hydrogen ions and oxygen-free radicals. Role of oxidative stress in heart failure subsequent to myocardial infarction. Google Scholar OpenURL Placeholder Text.

Effect of exercise training on antioxidant enzymes and cardiotoxicity of doxorubicin. Differential sensitivity of canine cardiac sarcolemmal and microsomal enzymes to inhibition by free radical induced lipid peroxidation. Redox modification of sodium—calcium exchange activity in cardiac sarcolemmal vesicles.

Effect of reduced oxygen intermediates on sarcolemmal muscarinic receptors from canine heart. Peroxidative damage to cardiac mitochondria: cytochrome oxidase and cardiolipin alterations.

Effect of lipid peroxidation on heart mitochondria oxygen consuming and calcium transporting capacities. Influence of mitochondrial radical formation on energy linked respiration. Protection of myocardial function and coronary vasculature by streptokinase. As an antioxidant, GSH efficiently scavenges ROS and nitrogen species, either directly or indirectly, by acting as a cofactor to support the activity of various enzymes [ ].

Furthermore, reduced levels of GSH trigger an imbalance in ROS levels, uncoupling of eNOS, and subsequent impairment of normal endothelial function, ultimately leading to endothelial dysfunction [ ].

Polyphenols, a diverse group of natural compounds abundantly present in plants, exhibit a range of biological activities that confer protection to heart function. These activities include antioxidant properties, anti-inflammatory effects, and improvements in endothelial dysfunction.

Structurally, polyphenols commonly feature one or more aromatic rings interconnected by hydroxyl groups. They can be broadly classified into two main families: flavonoids and non-flavonoids [ ].

Polyphenols are widely distributed in various dietary sources such as red wine, tea, fruits, and citrus fruits. Additionally, they can be derived from herbs, stems, and flowers [ , ].

Moreover, polyphenols play a crucial role in the defense systems of plants, aiding in reducing ultraviolet radiation and combating plant pathogens [ ]. In the context of CVDs, the intricate interplay between OS and inflammatory responses cannot be overlooked.

Polyphenols exert their antioxidant effects by engaging diverse signaling pathways and inhibiting the expression of NF-κB and its downstream signaling cascades.

Resveratrol RSV possesses notable antioxidant and anti-inflammatory properties, which contribute to its ability to upregulate eNOS function.

This upregulation of eNOS activity leads to a reduction in ROS levels, thereby alleviating OS and inhibiting lipid peroxidation. Moreover, RSV promotes NO synthesis and inhibits endothelial dysfunction, resulting in beneficial effects on CVDs such as PAH, AS, and MI [ ].

The cardiovascular protective effects of RSV are mediated through multiple molecular targets [ ]. For instance, RSV exhibits anti-atherosclerotic properties by reducing plasma triglyceride and LDL-cholesterol levels, inhibiting LDL oxidation, and increasing high-density lipoprotein-cholesterol [ ].

Notably, RSV activates SIRT1, a class III histone deacetylase, which is considered one of the most potent naturally occurring compounds with SIRT1 activating properties. The activation of SIRT1 leads to downstream effects on the FoxO transcription factor, a crucial antioxidant factor that helps maintain endothelial morphology.

The Akt pathway, regulated by SIRT1, plays a pivotal role in modulating FoxO activity. Activation of SIRT1 induces the expression of FoxO3a, which, in turn, promotes eNOS expression, thereby inhibiting intracellular ROS production and mitigating OS damage [ , ]. Resveratrol has also been found to confer protective effects on right ventricular dysfunction and pathological remodeling in mice with monocrotaline-induced PAH, contributing to improvements in pulmonary vascular architecture.

However, the extent of improvement may be limited. These beneficial effects could also be associated with the activation of specific sirtuin pathways, particularly SIRT1 and SIRT3 [ ]. SIRT1 serves as a target against endothelial dysfunction and can inhibit perivascular lipid incorporation and accumulation.

This process is regulated by increased phosphorylation of AMPK, which promotes SIRT expression and subsequently inhibits the expression of key regulators of adipogenesis, such as peroxisome proliferator-activated receptor γ PPARγ , essential for adipogenesis [ , ]. AMPK plays a crucial role in governing both catabolic and anabolic signaling pathways, and it also serves as a redox sensor and regulator, contributing to the preservation of normal cardiovascular function [ ].

Resveratrol-induced activation of AMPK has been shown to effectively reduce superoxide production in mitochondria or NOX, concurrently promoting the expression of antioxidant genes like SOD and eNOS, thereby exerting suppressive effects on oxidative stress [ ]. For instance, metformin, a drug used to treat hyperglycemia, triggers AMPK activation through the AMPK-PGC1α pathway in human umbilical vein endothelial cells HUVECs , leading to reduced mitochondrial ROS levels, the induction of SOD2, and the enhancement of mitochondrial biogenesis, effectively countering hyperglycemia-induced oxidative stress [ ].

Uncoupling protein 2 UCP2 represents a critical mitochondrial antioxidant protein, and its deficiency has been associated with increased oxidative stress and inflammation, which disrupts blood flow and promotes AS plaque progression.

Interestingly, overexpression of UCP2 has been shown to enhance AMPK phosphorylation in HUVECs, effectively inhibiting mitochondrial ROS production and attenuating the activity of the pro-inflammatory mediator forkhead box protein O1 FoxO1.

RSV exhibits protective effects against cardiovascular disease by activating various signaling pathways, including AMPK-SIRT1, AMPK-SIRT1-PGC-1α, AMPK-SIRT1-FoxOs, and AMPK-SIRT1-PPARα.

Activation of these pathways leads to the upregulation of antioxidant enzymes and the inhibition of NF-κB, thereby attenuating oxidative stress [ ]. Moreover, RSV demonstrates potent anti-inflammatory properties, which contribute to its cardioprotective effects by suppressing inflammation and oxidative stress.

It achieves this by inhibiting NF-κB activation. These signaling pathways collectively exert significant inhibitory effects on the development of cardiovascular disease [ , , , , ].

The PPAR plays a crucial role in regulating adipogenesis, and excessive lipid accumulation in adipose tissue is closely associated with an increased risk of cardiovascular disease [ ]. This activation leads to a reduction in the oxidative response of endothelial progenitor cells EPCs and promotes EPC re-endothelialization [ , ].

Moreover, RSV has been shown to activate the expression of Krüppel-like Factor 2 KLF2 in HUVECs, thereby providing protection against endothelial dysfunction.

Similarly, RSV-induced upregulation of KLF2 in EPCs has been shown to mitigate TNF-α-induced inflammatory injury and enhance EPC proliferation, adhesion, migration, angiogenesis, and nitric oxide NO bioavailability [ ]. Furthermore, RSV indirectly targets the Nrf2 pathway to confer cardiovascular protection.

Importantly, all these targets have been demonstrated to stimulate eNOS production and expression, thereby increasing NO bioavailability and reducing oxidative stress [ ].

Curcumin is a lipophilic polyphenolic substance with an orange-yellow color derived from the rhizome of a herb. It has been recognized for its significant role in the prevention and treatment of cardiovascular disease, primarily attributed to its antioxidant and anti-inflammatory properties [ , ].

Notably, curcumin has demonstrated anti-atherosclerotic effects, which can be ascribed to its ability to reduce elevated plasma cholesterol levels, inhibit LDL peroxidation, and attenuate lipid peroxidation [ ].

The antioxidant properties of curcumin are implicated in modulating various signaling pathways associated with cardiovascular health. By virtue of its antioxidant activity, curcumin exerts protective effects against oxidative stress-induced damage, thereby mitigating the progression of cardiovascular disease.

Additionally, curcumin possesses potent anti-inflammatory properties, which further contribute to its cardiovascular benefits.

The modulation of inflammatory signaling pathways by curcumin helps attenuate the inflammatory response and subsequent tissue damage observed in cardiovascular pathologies. Curcumin, a bioactive compound, exerts protective effects against OS in the cardiovascular system through multiple mechanisms.

One of the key pathways involved is the activation of the SIRT1-FoxO1 pathway and the PI3K-Akt survival pathway, which leads to the attenuation of OS, reduction of ROS levels, and restoration of cardiac SOD levels [ ].

Furthermore, curcumin demonstrates a capacity to mitigate mitochondrial oxidative damage induced by IR, thus reducing OS and improving postischemic cardiac function, myocardial infarct size, and myocardial apoptosis through the activation of SIRT1 signaling [ ]. Moreover, curcumin induces the activity of cell protective enzymes, including SOD, through Nrf2 signaling activation in cerebellar granule neuron models [ ].

Chlorogenic acid CGA , a prominent phenolic compound found in green coffee extracts and tea, exhibits significant antioxidant activity and plays a crucial protective role in cardiovascular disease [ ].

It also provides protection in patients with diabetic cardiomyopathy DCM by inhibiting glycosylation, modulating the PKCα- extracellular regulated protein kinases ERK signaling pathway, and exerting antioxidant effects [ , ].

In experimental models, CGA has shown considerable reductions in pro-inflammatory cytokines, MI size, OS, and mitochondrial respiratory defects, while simultaneously enhancing antioxidant enzyme activity to protect the damaged myocardium [ , ].

CGA exhibits protective effects against OS damage in endothelial cells exposed to hypochlorous acid, thereby improving vascular function. These effects are primarily attributed to the increased production of NO to prevent endothelial dysfunction and the induction of heme oxygenase-1 Hmox-1 [ ].

Similarly, CGA enhances NO formation in acidified saliva and reduces the intensity of free radicals [ ]. Salvianolic acid, a natural polyphenolic compound derived from Salvia miltiorrhiza , exhibits significant protective effects against cardiovascular disease, primarily attributed to its antioxidant properties.

Numerous studies have reported the ability of salvianolic acid to delay the development of ischemia by promoting angiogenesis, reducing infarct size, and improving post-infarction contractile function in animal models of MI [ , ].

Salvianolic acid A Sal A pretreatment has demonstrated its ability to attenuate arsenic trioxide ATO -induced structural and functional damage to cardiac mitochondria.

By reducing mitochondrial ROS overproduction, Sal A exerts a protective effect against ATO-induced cardiotoxicity in the heart.

This protection is primarily attributed to the activation of the expression level of PGC-1α, which plays a crucial role in maintaining normal mitochondrial function [ ]. Furthermore, Sal A has shown efficacy in preventing myocardial injury induced by lipotoxicity.

Sal A treatment has also been associated with the activation of signaling pathways that promote beneficial effects in adipose tissue and vascular protection. Activation of AMPK signaling and SIRT1 signaling contributes to increased white adipose tissue browning and reduced lipid accumulation [ ].

This suggests that Sal A may be a potential candidate compound for the prevention of ischemic tissue injury in cardiovascular disease [ ]. In experiments related to diabetes-associated macrovascular and renal injury, Sal A exhibits potential as an Nrf2 modulator with a protective effect on the vasculature.

Salvianolic acid B Sal B , one of the major active components derived from Salvia miltiorrhiza , exhibits inhibitory effects on the proliferation and migration of VSMCs. This inhibition is mediated by the induction of Nrf2 and HO-1 pathway expression.

In addition, Sal B has been shown to attenuate acute myocardial ischemic injury induced by subcutaneous ISO administration in rats. This protective effect is achieved through the inhibition of intracellular ROS production, enhancement of mitochondrial membrane potential, and promotion of mitochondrial autophagy [ ].

Tea is known to contain a rich array of biologically active compounds that confer beneficial effects on CVDs. Among these compounds, the polyphenols, particularly catechins and their derivatives such as catechin, epicatechin, and epigallocatechin gallate EGCG , along with other polyphenols like gallic acid, chlorogenic acid, and various flavonoids, play a significant role [ ].

The mechanisms underlying the preventive effects of tea polyphenols on CVDs involve multiple pathways. This activation of Nrf2 signaling by EGCG exerts antioxidant effects, improves blood lipid levels, and enhances SOD activity [ ].

Magnoliae officinalis cortex, commonly referred to as "Houpo," is the dried bark of Magnolia officinalis and is widely utilized in traditional Chinese medicine [ ]. This botanical resource is characterized by its abundance of bioactive compounds, including Honokiol HKL.

Notably, Honokiol has been recognized for its potential in conferring cardiovascular protection by virtue of its capability to scavenge free radicals and exert antioxidant effects within the body. HKL is a naturally occurring biphenol compound that exhibits notable potential in blocking and ameliorating myocardial hypertrophy [ ].

This effect is primarily attributed to HKL's ability to activate SIRT3, leading to increased levels and enhanced activity of this protein. Activated SIRT3, in turn, augments the antioxidant capacity of SOD and promotes the activation of PGC-1α.

These actions collectively contribute to the reduction of ROS synthesis and mitigating OS within the heart.

In studies involving HUVECs, HKL effectively inhibits palmitic acid PA -induced endothelial dysfunction. HKL achieves this by attenuating IκB phosphorylation and reducing the expression of NF-κB subunits p50 and p65 [ ]. Additionally, HKL demonstrates regulatory effects on iNOS, eNOS, and NO production, which collectively contribute to reducing endothelial cell injury and apoptosis [ ].

Furthermore, HKL exerts modulatory effects on cardiac mitochondrial fatty acid respiration and atherosclerotic plaque formation. These effects are primarily mediated through the activation of AMPK and enhanced SOD activity [ , ].

The fruit extract of Schisandra chinensis SC and its bioactive lignan component exhibit notable therapeutic potential in the management of OS-related CVDs. Their beneficial effects encompass the activation of antioxidant defense systems, inhibition of pro-oxidant signaling pathways, and modulation of NO expression [ ].

Treatment with schisandrol A, a bioactive component of SC, exhibited a protective effect in mice with acute MI. It significantly reduced infarct size, preserved cardiac function, and improved biochemical parameters and cardiac pathological changes.

Another lignan found in SC, gomisin J, was shown to enhance the phosphorylation of eNOS and facilitate the translocation of eNOS in the cytoplasm of the rat thoracic aorta. Additionally, the dibenzocyclooctadiene lignan known as α-Iso-cubebene, present in SC, demonstrated the ability to inhibit high mobility group box-1 protein -induced monocyte to macrophage differentiation by suppressing ROS production in monocytes.

This attenuation of vascular inflammation, coupled with endothelial proliferation associated with vascular injury, highlights the potential anti-inflammatory effects of α-Iso-cubebene [ ]. Sesame seeds and their bioactive lignan components, namely sesamin and sesamol, have been implicated in reducing the risk of cardiovascular disease by modulating OS and inflammation.

Studies have shown that sesamol and sesamin effectively mitigate LPS-induced inflammation and OS factors in rats. Additionally, they prevent lipid peroxidation and restore SOD activity, thereby exerting protective effects [ ].

Sesamin has demonstrated cardioprotective properties against DOX-induced cardiotoxicity and OS damage. It accomplishes this by activating the expression of Mn-SOD protein and stimulating SIRT1 activity [ ]. Long-term sesamin treatment has been observed to improve arterial dysfunction in SHR by upregulating eNOS expression while downregulating p22 phox and p47 phox expression in NADPH oxidase [ ].

Furthermore, sesamin exerts its impact on reducing cardiovascular disease risk by inhibiting fatty acid synthesis and oxidation, cholesterol synthesis and absorption, and maintaining macrophage cholesterol homeostasis.

Phillyrin and forsythin are bioactive constituents derived from the fruit of Forsythia suspensa, a medicinal plant. Moreover, phillyrin pretreatment has been shown to significantly improve cardiac function, reduce ROS production, and mitigate the inflammatory response [ ].

Forsythin, on the other hand, has been found to suppress LPS-induced inflammation in RAW This anti-inflammatory activity is attributed to its ability to inhibit JAK-STAT and p38 MAPK signaling pathways, as well as reducing ROS generation [ ].

Cinnamic acid CA is an organic acid obtained from cinnamon bark or benzoin and is known for its diverse range of biological activities, including antioxidant and anti-inflammatory properties.

Notably, CA has been found to exhibit inhibitory effects on PDGF-BB-induced proliferation of VSMCs. This inhibition is achieved through the upregulation of p21 and p27 protein expression levels, both of which are key regulators of cell cycle progression and proliferation [ ].

CA and cinnamaldehyde have demonstrated protective effects against ischemic myocardial injury induced by ISO in a rat model. This protection is attributed to their ability to enhance the anti-OS effect of NO and increase SOD activity in cardiac tissue [ ]. Additionally, both CA and cinnamyl alcohol exhibit vasodilatory effects by activating the NO-cGMP-PKG pathway, while also inhibiting Rho-kinase [ , ].

Ferulic acid FA , a derivative of cinnamic acid, is an important active ingredient found in various Chinese medicines, including the root of Angelica sinensis Oliv. FA exhibits notable protective effects, particularly against OS, inflammation, vascular endothelial damage, and platelet aggregation associated with CVDs.

This ultimately mitigated OS in cardiac myocytes [ ]. This inhibition led to a reduction in succinate levels, thereby mitigating excessive intracellular ROS production and OS [ ]. Syringic acid SA is a naturally occurring compound synthesized in plants through the shikimate pathway.

It can be sourced from various plants, including Conyza canadensis L. Cronq in the Asteraceae family and Rhododendron dauricum L. in the Rhododendron family. The shikimate pathway serves as the primary route for SA biosynthesis in plants.

SA exhibits cardioprotective effects in a rat model of MI induced by ISO. These effects may be attributed to its ability to counteract lipid peroxidation and enhance endogenous antioxidant systems, such as increasing the content of reduced GSH [ ]. Similarly, syringaldehyde, another compound with antioxidant and anti-inflammatory properties, also demonstrated cardioprotective effects in the ISO-induced MI model [ ].

Furthermore, the combination of SA and RSV referred to as combination exhibited cardioprotective abilities against ISO-induced cardiotoxicity in rats.

This effect was achieved by inhibiting the NF-kB and TNF-α pathways, suppressing lipid peroxidation, reducing NF-kB and TNF-α mRNA expression, and increasing the activities of SOD and CAT [ ].

Oleanolic acid OA is a pentacyclic triterpenoid that is widely present in Chinese medicine. It can be isolated and extracted from various sources, including the whole herb of Swertia plants in the Gentianaceae family or the fruit of Ligustrum lucidum.

OA exhibits beneficial effects on cardiovascular protection, including hypolipidemic, anti-AS activity, and hypotensive effects [ , ].

OA also attenuates mitochondrial damage, restores NO production, and enhances the activities of SOD and CAT [ ]. Furthermore, OA demonstrates its ability to attenuate cardiac remodeling during aging by modulating mitochondrial autophagy and ameliorating mitochondrial ultrastructural abnormalities [ ].

Baicalin BA is a bioactive flavonoid that can be isolated from the roots of the traditional herb Scutellaria baicalensis Georgi.

It constitutes approximately BA has been extensively studied for its antioxidant and anti-inflammatory properties, particularly in the context of cardiovascular disease disorders [ , ].

The cardioprotective effects of BA are attributed to its ability to attenuate NF-κB activity and inhibit inflammatory cell infiltration. Additionally, BA exerts its beneficial effects by suppressing the production of pro-inflammatory cytokine TNF-α, scavenging ROS, and enhancing the endogenous antioxidant capacity [ ].

BA, a bioactive flavonoid derived from the roots of Scutellaria baicalensis Georgi, exhibits diverse effects on cardiovascular health. It demonstrates antiproliferative and migratory properties in VSMCs and effectively attenuates carotid artery neointimal hyperplasia.

These effects may be mediated, at least in part, by the upregulation of smooth muscle 22 alpha SM22α expression, suppression of ROS production, and inhibition of ERK phosphorylation [ ]. Furthermore, BA mitigates hypoxia-induced pulmonary vascular remodeling and exerts an antiproliferative effect on PASMCs.

BA also attenuates Ang II-induced endothelial dysfunction and oxidative stress by promoting endothelial vasodilation, inhibiting apoptosis of HUVECs, and enhancing antioxidant capacity. In the context of hyperglycemia-induced cardiovascular malformations, BA administration effectively inhibits ROS and induces autophagy, thereby mitigating developmental abnormalities during early chick embryonic development [ ].

Additionally, BA treatment effectively reduces atherosclerotic lesion size and lipid accumulation in carotid arteries of AS rabbits. This effect is mediated through the PPARγ-LXRα signaling pathway, which enhances the expression of ATP-binding cassette transporter A1 ABCA1 and ABCG1.

Quercetin, a widely distributed flavonoid in plants, exhibits multiple mechanisms that contribute to its potential in reducing the risk of OS-related CVDs. It exerts its effects through various pathways, including the reduction of ox-LDL levels, inhibition of OS, mitigation of endothelial dysfunction, protection of endothelial function, suppression of adhesion molecules and inflammatory markers, and inhibition of platelet aggregation [ ].

The administration of quercetin has been shown to exhibit beneficial effects on endothelial dysfunction and AS in various experimental models. In SHR rats, quercetin treatment suppressed endothelial dysfunction by downregulating NADPH oxidase activity in VSMCs and enhancing eNOS activity [ , ].

In mice fed a HFD, quercetin demonstrated anti-endothelial dysfunction and AS effects, which were mediated by increased HO-1 protein expression and improved NO bioavailability [ ]. This was evidenced by the reduction in ROS production, increased expression and activity of DDAHII leading to decreased ADMA levels, and subsequent inhibition of eNOS uncoupling, ultimately resulting in increased NO content [ ].

Quercetin exerts protective effects on the heart through various signaling pathways. Quercetin also activates SIRT5, leading to the desuccinylation of IDH2, which helps maintain mitochondrial homeostasis, attenuate inflammatory responses and OS damage, and improve cardiac function in a mouse model of myocardial fibrosis and heart failure induced by transverse aortic constriction TAC [ ].

Furthermore, quercetin inhibits OS and promotes mitochondrial homeostasis, thereby reducing VSMCs apoptosis and mitigating vascular calcification [ ]. The protective effect of quercetin against ISO-induced myocardial ischemia may also involve the inhibition of calcium influx [ ].

Lignans, derived from traditional Chinese herbs, have been recognized for their potential cardioprotective effects mediated through multiple signaling pathways. These compounds exhibit antioxidant and anti-inflammatory properties and have shown the ability to alleviate endothelial dysfunction.

The mechanisms underlying the cardioprotective effects of lignans involve their antioxidant activity and modulation of inflammatory responses. Furthermore, lignans have been found to improve endothelial function. Lignans, derived from traditional Chinese herbs, have emerged as potential cardioprotective agents through their modulation of various signaling pathways.

Lignocaine, a specific lignan compound, has been shown to mitigate OS damage and inflammatory factors in HUVECs by inhibiting the STAT3 pathway. This inhibition results in reduced ROS production and inhibition of STAT3 activation, leading to a decrease in the production of oxysterols and hydroxylated fatty acids, which are implicated in the pathogenesis of atherosclerosis and other CVDs [ ].

Lignans also play a crucial role in mitigating the proliferation and apoptosis of VSMCs in atherosclerosis. Another lignan compound, luteolin, has demonstrated the ability to attenuate OS and inflammatory responses in HUVECs induced by TNF-α.

This pathway holds promise as a potential target for cardiac protection [ ]. Lignans have also been found to alleviate inflammatory phenotype and OS induced by high glucose HG in various cellular models.

These effects are mediated through inhibition of the NF-κB pathway and activation of the Nrf2 signaling pathway, highlighting the potential of lignans in preventing diabetic cardiovascular complications [ ]. Moreover, lignans exhibit protective effects against cardiac fibrosis, hypertrophy, and dysfunction induced by streptozotocin in mice by modulating these pathways [ ].

Another important protein involved in the regulation of oxidative stress is Sestrin2, which plays a role in activating the antioxidant signaling pathway mediated by Nrf2. In a rat model of hypoxic pulmonary hypertension HPH , luteolin has been demonstrated to reduce pulmonary vascular remodeling and improve pulmonary vascular endothelial cell function.

Luteolin treatment leads to a reduction in hypoxia-induced HIF-2α expression, which subsequently promotes the expression of nitric oxide NO.

Additionally, luteolin treatment enhances the expression of endothelial nitric oxide synthase eNOS without increasing its activity. Luteolin treatment leads to a reduction in hypoxia-induced HIF-2α expression, which subsequently promotes the expression of NO. Additionally, luteolin treatment enhances the expression of eNOS without increasing its activity.

In contrast, another study investigating the effects of luteolin on monocrotaline MCT -induced PAH in rats revealed different findings. Naringin, a natural flavonoid found in various herbs, exhibits protective effects against OS-induced heart damage and cardiovascular dysfunction.

Its antioxidant activity enables scavenging of free radicals and mitigating OS-related damage [ ]. In HUVECs, naringin attenuates autophagy by inhibiting the activation of the PI3K-Akt-mTOR signaling pathway, thereby alleviating dysfunction induced by HG and HFD conditions [ ].

Furthermore, naringin improves mitochondrial and cardiac dysfunction induced by HFD, reduces blood lipid concentrations, and mitigates OS [ ]. In hypercholesterolemic rats, naringin treatment attenuates vascular OS and endothelial dysfunction by reducing the protein expression of lipoprotein receptor-1, NADPH oxidase subunits, and iNOS [ ].

Naringenin treatment demonstrates significant reduction of sodium arsenite-induced cardiotoxicity in rats. Naringenin effectively prevents abnormal Na—K-ATPase activity induced by arsenic toxicity, potentially through its membrane stabilizing properties.

Naringenin also upregulates the expression levels of Nrf-2 and HO-1, increases myocardial mitochondrial enzyme activity, and improves the structural morphology of the heart [ ].

Alkaloids are a class of nitrogenous organic compounds characterized by complex cyclic structures and basic properties. They are widely distributed in dicotyledonous plants. One notable alkaloid is berberine BBR , which is isolated from the Chinese herb Huanglian and serves as the main active ingredient.

Studies have demonstrated the significant role of BBR in post-MI myocardial cell injury and its ability to improve ventricular remodeling and OS injury in a mouse model of myocardial ischemia. Furthermore, BBR mediates SIRT1 to inhibit the expression of p66Shc and enhance the activity of CAT, SOD, and GSH-PX.

This mechanism reduces MDA levels and ameliorates doxorubicin-induced cardiomyopathy in rats [ ]. By upregulating Klotho expression and downregulating SIRT1 expression, BBR exerts antioxidant effects and prevents cardiac aging [ ]. Saponins, a diverse group of compounds, serve as the principal bioactive components in numerous Chinese medicines, exhibiting various pharmacological activities, including antioxidative stress effects.

Additionally, studies have demonstrated that AS-IV significantly reduces DOX-induced cardiomyocyte death, apoptosis, and cardiac insufficiency by inhibiting NOX2- and NOX4-mediated oxidative stress [ ]. Ginsenoside, the major active constituent of ginseng, possesses diverse pharmacological effects, including antioxidant properties.

Additionally, ginsenoside Rg1 inhibits caspase-3 expression, restores Bcl-xL expression, alleviates oxidative stress, and protects against myocardial injury in diabetic rats [ ].

Quinones, primarily sourced from natural plants belonging to the Rubiaceae, Polygonaceae, Leguminosae, Rhamnaceae, and Liliaceae families, exhibit a diverse array of pharmacological effects. Treatment with Tanshinone IIA reduces PERK and eukaryotic translation initiation factor 2α expression in cardiomyocytes, thereby ameliorating ER stress, reducing cardiomyocyte apoptosis, mitigating ROS production, and attenuating oxidative stress, consequently inhibiting MI and enhancing myocardial function [ ].

Polysaccharides, which are widely distributed in animals, plants, and microorganisms, exhibit diverse biological activities, including antioxidant and immunomodulatory effects. Among them, Lycium barbarum polysaccharide LBP serves as the principal bioactive component in Lycium barbarum and contributes significantly to its medicinal properties, particularly its antioxidant activity.

Moreover, LBP demonstrates anti-apoptotic effects and mitigates oxidative stress [ ]. Notably, LBP administration in a rat model of heart failure resulted in a significant reduction in plasma lipid peroxidation levels, as indicated by decreased MDA content [ ].

Furthermore, LBP supplementation exhibited a noteworthy impact on ameliorating DOX-induced acute cardiotoxicity by increasing the activities of SOD and GSH-Px and reducing myocardial MDA levels [ ] Fig.

Herbal monomers such as polyphenols, flavonoids, alkaloids, saponins, quinones and polysaccharides inhibit the expression of ROS through various signaling pathways and reduce the damage caused by OS to the organism.

This can be reflected by the upregulation of SOD, GPX, CAT, GSH, NO, eNOS phosphorylation and downregulation of inflammation, ROS, vascular remodeling, ECs proliferation and migration. As highlighted in this article, maintaining normal physiological levels of ROS is critical for the treatment of OS-related CVDs.

First, we briefly review the sources of ROS production, including NOXs, eNOS, ER stress, mitochondrial ETC leakage, and peroxisomes, with eNOS uncoupling leading to impaired protective NO synthesis and increased OS being particularly significant in CVDs.

Second, OS-related signaling pathways are equally important for the promotion of PAH, AS and MI. In addition, it is worth noting the interaction of the inflammatory response with OS in the disease process. Probucol is the only antioxidant drug approved by Food and Drug Administration, and it also shows a very powerful therapeutic effect in CVDs, but it has gradually faded out of the clinical treatment of CVDs because of its side effects such as gastrointestinal discomfort, diarrhea, ventricular tachycardia and severe ventricular arrhythmias [ , ].

Although antioxidants have not been widely used in the treatment of CVDs to date, they should still be taken seriously, especially natural antioxidants, which remain indispensable as potential therapeutic agents for the treatment of CVDs. Clinical studies have found that natural antioxidants such as RSV, tea polyphenols, BA and quercetin have significant efficacy in the prevention and treatment of CVDs, and have the advantages of low toxicity and fewer adverse effects, which have become a hot spot for research at home and abroad [ , , ].

The Chinese herbal monomer antioxidant therapy mentioned in detail in this article can help prevent and treat PAH, AS and MI. Therefore, it is undeniable that herbal monomers are widely used for the prevention and treatment of various diseases due to their remarkable efficacy and high safety.

However, herbal monomers targeting OS through their powerful antioxidant therapeutic capacity as a preventive and therapeutic approach to CVDs may provide limited additional benefit. First, because the antioxidant effects of some herbal monomers mentioned in the current paper have only been evaluated in preliminary pharmacological studies, without further research or in-depth study of their molecular mechanisms.

Secondly, data on pharmacokinetic and clinical studies of these reported herbal monomers are scarce, and studies on toxicity and its target organs are hardly reported.

Therefore, it is essential that more work should be invested in the future to study the side effects and toxicity of these herbal monomers. Meanwhile, we have little access to data from clinical studies of herbal monotherapy for OS-associated CVDs. Therefore, researchers should be encouraged to further investigate the clinical studies of herbal monomers on CVDs and the side effects and toxicity studies after treatment with herbal monomers to evaluate the actual therapeutic effects of these herbal monomers in humans.

In addition, one of the drawbacks of herbal monomers cannot be ignored is their low bioavailability. Perhaps we can consider developing new dosage forms for them to improve their bioavailability or new dosage forms that can reduce their toxicity.

In conclusion, the development of safe and effective natural drugs for antioxidant therapy is an important goal for the prevention and treatment of CVDs in the future.

Forman HJ, Zhang H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov. Article CAS PubMed PubMed Central Google Scholar. Steven S, Frenis K, Oelze M, Kalinovic S, Kuntic M, Bayo Jimenez MT, et al.

Vascular inflammation and oxidative stress: major triggers for cardiovascular disease. Oxid Med Cell Longev. Winiarska A, Knysak M, Nabrdalik K, Gumprecht J, Stompór T. Inflammation and oxidative stress in diabetic kidney disease: the targets for SGLT2 inhibitors and GLP-1 receptor agonists.

Int J Mol Sci. Article PubMed PubMed Central Google Scholar. Wójcik P, Gęgotek A, Žarković N, Skrzydlewska E. Oxidative stress and lipid mediators modulate immune cell functions in autoimmune diseases. Senoner T, Dichtl W. Oxidative stress in cardiovascular diseases: still a therapeutic target?

Xu D, Hu Y-H, Gou X, Li F-Y, Yang X-Y-C, Li Y-M, et al. Oxidative stress and antioxidative therapy in pulmonary arterial hypertension.

Kattoor AJ, Goel A, Mehta JL. LOX regulation, signaling and its role in atherosclerosis. Song R, Dasgupta C, Mulder C, Zhang L.

MicroRNA controls mitochondrial metabolism and protects heart function in myocardial infarction. Xiao W, Loscalzo J. Metabolic responses to reductive stress. Antioxid Redox Signal. Sies H. Oxidative stress: a concept in redox biology and medicine.

Redox Biol. Villalpando-Rodriguez GE, Gibson SB. Reactive oxygen species ROS regulates different types of cell death by acting as a rheostat.

Slimen IB, Najar T, Ghram A, Dabbebi H, Ben Mrad M, Abdrabbah M. Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review. Int J Hyperthermia. Article CAS PubMed Google Scholar. Vatner SF, Zhang J, Oydanich M, Berkman T, Naftalovich R, Vatner DE.

Healthful aging mediated by inhibition of oxidative stress. Ageing Res Rev. Forrester SJ, Kikuchi DS, Hernandes MS, Xu Q, Griendling KK. Reactive oxygen species in metabolic and inflammatory signaling. Circ Res.

Nolfi-Donegan D, Braganza A, Shiva S. Mitochondrial electron transport chain: oxidative phosphorylation, oxidant production, and methods of measurement.

Zhao R-Z, Jiang S, Zhang L, Yu Z-B. Mitochondrial electron transport chain, ROS generation and uncoupling review. Int J Mol Med. Zhao S, Zang G, Zhang Y, Liu H, Wang N, Cai S, et al. Biosens Bioelectron. Mittler R. ROS are good. Trends Plant Sci. Wang Y, Hekimi S. Understanding ubiquinone.

Trends Cell Biol. Hahner F, Moll F, Schröder K. NADPH oxidases in the differentiation of endothelial cells. Cardiovasc Res. Georgiou CD, Margaritis LH.

Oxidative stress and NADPH oxidase: connecting electromagnetic fields, cation channels and biological effects.

Int J Mole Sci. Article Google Scholar. Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: oxidative eustress. Reyhani A, McKenzie TG, Fu Q, Qiao GG. Fenton-chemistry-mediated radical polymerization. Macromol Rapid Commun. Halliwell B, Adhikary A, Dingfelder M, Dizdaroglu M.

Cardiovascular diseases CVDs Oxidatkve diverse diseasses mechanisms with interconnected oxidative stress and inflammation as one of the common etiologies which result in the Fat burn cardio and development of Boost energy for workouts plaques. In this review, we carriovascular this strong Oxidative stress and cardiovascular diseases riseases Weight loss and sports injuries stress, inflammation, and CVD. In part, we focus on the laboratory biomarkers and physiological tests for the evaluation of oxidative stress status and inflammatory processes. The impact of a healthy lifestyle on CVD onset and development is displayed as well. Furthermore, the differences in oxidative stress and inflammation are related to genetic susceptibility to cardiovascular diseases and the variability in the assessment of CVDs risk between individuals; Omics technologies for measuring oxidative stress and inflammation will be explored. Diweases of Oxidative stress and cardiovascular diseases and Biophysics, University of Cardioascular, Kalyani, India. You can also search for this editor in PubMed Google Scholar. Institute of Cardiovascular Sciences, St Boniface Hospital, Albrechtsen Research Centre, Winnipeg, Canada. Translational Health Science and Technology THSTIDepartment of Biotechnology, Faridabad, India. Provides interesting facts, real laboratory data and tips for designing experiments in the specified areas.

Thomas Münzel, Tommaso Gori, Rosa Maria Bruno, Stefano Taddei, Is an stress a therapeutic target Oxidative stress and cardiovascular diseases cardiovascular disease?

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when NO is insufficiently produced or too rapidly scavenged. Other Stres such as the dismutation product of superoxide hydrogen peroxide and hypochlorous acid cannot be considered as free radicals, but have a powerful oxidizing capacity, which will further contribute to oxidative stress within vascular tissues.

An unbalanced production of nitric oxide and superoxide secondary Understanding your metabolic rate cardiovascular risk factor exposure leads to inappropriate Mental clarity exercises of superoxide by the nicotinamide dinucleotide phosphate oxidase, xanthine oxidase, sterss the diseses.

Superoxide dieeases reacts with nitric oxide sfress form the highly reactive strss peroxynitrite, which causes disdases dysfunction through different mechanisms including nitric oxide synthase uncoupling secondary to BH 4 oxidation insert Oxidative stress and cardiovascular diseases, tyrosin nitration of Oxidqtive prostacyclin synthase PGI 2 SWeight loss and sports injuries subsequent inhibition of PGI 2 formation and by inhibiting the activity of Cosmetic smile makeovers soluble guanylate cyclase Antioxidant-rich antioxidant-rich supplements and therefore Pre-workout supplements oxide signalling.

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patients cardioovascular whom oxidative stress cardiovazcular be demonstrated have a worse prognosis when compared with disseases with low stresx no vitamin C effects 5 Figure 2. This finding strengthens not only the concept that Diabetic-friendly lunch recipes stress is Weight loss and sports injuries the key player in determining the degree shress endothelial dysfunction, Oxidxtive also that the prognosis of patients with established coronary artery diweases is tightly determined by these processes.

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The most important superoxide sources comprise the so-called nicotinamide dinucleotide phosphate NADPH oxidase, the xanthine oxidase, mitochondria, and, under certain conditions, the endothelial NOS. The NADPH oxidase is a superoxide-producing enzyme, first characterized in neutrophils, but also expressed in endothelial and smooth muscle cells as well as in the adventitia.

This enzyme consists of at least five isoforms NOX Figure 3. The nicotinamide dinucleotide phosphate oxidase NOX isoforms being expressed in vascular tissue include NOX1, NOX2, NOX4, and NOX5. The NOX1, NOX2, and NOX4 isoforms require the subunit p22phox to form functional reactive oxygen species-generating nicotinamide dinucleotide phosphate oxidase enzymes; this is, however, not the case for NOX5.

The NOX1 nicotinamide dinucleotide phosphate oxidase associates with two cytosolic factors p47phox and NOXA1 as well as a small-molecular-weight molecule Rac; NOX2 is regulated by p47phox and p67phox, whereas NOX4 has no regulatory subunits; NOX5 is unique because its activity is regulated by calcium.

The oxidizing superoxide is generated via an electron shuttle from nicotinamide dinucleotide phosphate to oxygen, which is why one calls it the nicotinamide dinucleotide phosphate oxidase.

ER, endoplasmic reticulum; VEGF, vascular endothelial growth factor; VSMC, vascular smooth muscle cells. Figure from Schulz and Munzel. Under certain conditions e. upon angiotensin II stimulationthe activity of the enzyme is increased in endothelial and smooth muscle cells, suggesting that in the presence of an activated renin—angiotensin system either local or circulatingvascular dysfunction due to increased vascular superoxide production is likely to be expected.

Experimental hypercholesterolaemia has been shown to be associated with an activation of the NADPH oxidase, 6 and in human saphenous veins of patients with coronary artery disease, a close association has been shown between endothelial dysfunction, clinical risk factors, and the activity of this enzyme.

Interestingly, ACE activity and therefore local angiotensin II concentrations are increased in the shoulder region of atherosclerotic plaques, and inflammatory cells are capable of producing large amounts of angiotensin II along with superoxide.

Evidence for an activation of this enzyme in the vasculature has also been derived from multiple experimental animal models of hypertension as well as in different forms of diabetes mellitus.

Xanthine oxidoreductase catalyses the sequential hydroxylation of hypoxanthine to yield xanthine and uric acid. The enzyme can exist in two forms that differ primarily in their oxidizing substrate specificity.

Alternatively, increased cholesterol levels might trigger the release of xanthine oxidase e. from the liver into the circulation where it binds to endothelial glycosaminoglycans.

Mitochondrial superoxide generation represents a major intracellular source of ROSs under physiological conditions. Mitochondrial superoxide levels are highly governed by the respiratory rate and by the activity of the manganese superoxide dismutase located in the matrix of the organelle.

Stimulation of endothelial cells with angiotensin II, oxLDL, lipid peroxidation products, high glucose levels, free fatty acids, protein kinase C, and cyclic strain is able to stimulate mitochondrial superoxide production, 13 and an inappropriately high mitochondrial ROS production has been shown in a number of settings.

In most situations in which endothelial dysfunction due to increased oxidative stress is encountered, the expression of the NOS has been shown to be paradoxically increased.

The demonstration of endothelial dysfunction in the presence of increased expression of NOS indicates that the capacity of the enzyme to produce NO may be limited, a concept that fits well with the observation that the NOS itself can be a superoxide source.

Interestingly, downregulation of GTP-CH-I and DHFR, resulting in decreased vascular BH 4 levels and NOS uncoupling, can be observed in the setting of angiotensin II-induced hypertension and diabetes mellitus.

Pre-clinical studies treating diabetic or hypercholesterolaemic animals with statins and AT1-receptor blockers demonstrated that these compounds are able to inhibit the activity and expression of the NADPH oxidase and recouple NOS by preventing BH 4 oxidation and the downregulation of BH 4 synthesizing enzymes.

Similarly, vitamin C is able to recycle BH 4 from its oxidized form Figure 1which suggests that the antioxidant effect of this molecule might also be mediated by mechanisms other than direct superoxide scavenging.

Increased concentrations of the arginine-analogue ADMA in cultured endothelial cells or in patients with endothelial dysfunction are associated with increased ROS production.

Interestingly, the activity of enzymes responsible for the synthesis of ADMA such as the S -adNOSylmethionine-dependent protein arginine methyltransferase and that of ADMA-hydrolysing enzymes such as dimethylarginine dimethylaminohydrolase is redox-sensitive.

Taken together, the results of the in vitro and pre-clinical data strongly suggest that increased vascular production of ROS contributes substantially to the initiation and continuation of the atherosclerotic process, suggesting that manoeuvres that reduce oxidative stress in vascular tissue should in general beneficially influence not only vascular function, but also the prognosis of patients with cardiovascular disease.

A wide range of prospective cohort studies confirm the above considerations. For instance, the lower cardiovascular mortality observed in Mediterranean populations when compared with Northern European countries has been attributed to differences in the intake of antioxidant-rich foods and beverages.

The Zutphen Elderly study, conducted in elderly men without prior history of cardiovascular disease, provided the first evidence of a reduced mortality from coronary heart disease in patients with high flavonoid intake, which was confirmed after adjustment for traditional cardiovascular risk factors and antioxidant vitamin intake.

bottom tertile of antioxidant vitamins intake of coronary heart disease in a meta-analysis of 15 prospective cohort studies involving participants.

Adapted from Ye and Song. Despite these limitations, the above results prompted great enthusiasm, reinforcing the role of ROS as pathophysiological mechanism and as a possible therapeutic target.

Perhaps, the most insidious pitfall in cohort studies is the difficulty in correctly evaluating the importance of confounding factors. For example, in one of the cornerstones of prospective studies that demonstrated the beneficial effect of vitamin C on total mortality, the EPIC study, 25 no adjustment was made for two informative and easily obtainable parameters of socio-economic status and lifestyle such as social class and physical activity.

The confounding power of socio-economic status is nevertheless very difficult to quantify, and elimination of this source of error, in order to exclude the hypothesis that high antioxidant intake is simply the marker of a healthier lifestyle, requires robust and accurate study design and statistical analysis.

Since great expectations were awakened by the above epidemiological studies, a number of interventional trials were conducted between andmainly administering vitamin E, in the synthetic or natural form, ß-carotene, and vitamin C, alone or in combination, and at different dosages.

Clinical trials gave heterogeneous outcomes: some studies showed a benefit of vitamin E supplementation in the secondary prevention of cardiovascular disease 27 and of vitamin E plus C supplementation in slowing carotid intima—media thickening in hypercholesterolaemic patients.

The data were pooled together in a meta-analysis, 29 which demonstrated a substantial lack of efficacy for different doses of ß-carotene and vitamin E in diverse population groups Figure 5.

Further attempts have been made with the supplementation of folic acid, which, as discussed earlier, might compensate for the oxidation of the NOS coenzyme BH 4. However, also these studies did not show a prognostic impact of this type of supplementation. Thus, the AHA Committee for Nutrition, Physical Activity, and Metabolism discouraged the use of antioxidant supplementation for the prevention of cardiovascular disease.

Adapted from Vivekananthan et al. In summary, interventional trials did not confirm whether the oxidative stress modification hypothesis is relevant in the clinical setting and, more importantly, did not allow concluding that pharmacological correction of the redox status could be used as a safe and effective therapeutic strategy.

Moreover, the discrepancy between mechanistic and cohort studies and randomized clinical trials has created, if possible, even greater confusion. It might well be that the antioxidants used were intrinsically flawed.

Or else, it could be argued that interventional trials conducted so far were not adequately designed, both for conceptual and for methodological reasons.

One crucial issue is: what population is likely to benefit from antioxidant supplementation? The majority of the studies enrolled patients at high risk or who previously experienced a myocardial infarction. These conditions are characterized by established atherosclerotic damage, which is unlikely to regress with antioxidant treatment.

In contrast, even in healthy subjects, equalling the positive effects of a lifelong high vegetable and fruit diet simply by a few years-long antioxidant supplementations appears to be a very ambitious endpoint.

Moreover, it is still not clear whether the benefit of antioxidant supplementation depends on baseline antioxidant status, because reliable, simple, and easily available biomarkers of oxidative stress, suitable for large population studies, are still unavailable.

Instead, low concentrations of some ROSs, particularly hydrogen peroxide, are likely to play a role as physiological intracellular mediators in fundamental processes such as cell growth and angiogenesis, and an important role of ROS has also been shown in protective mechanisms such as preconditioning.

Methodological issues also need to be carefully acknowledged before dismissing the antioxidant hypothesis: for instance, the role of trial design issues, choice of outcome measures, duration of treatment, populations under study, and concomitant therapy should not be underestimated.

Examination of these aspects would require a more detailed discussion, given elsewhere; 3536 just to limit to some examples, the rate constant between vitamin C and superoxide is 10 5 lower than that between superoxide and NO, and supraphysiological levels of ascorbic acid in the range of 10 mM, i.

In addition, oral administration of vitamin C might not allow achieving biologically active levels, and finally, treatment with vitamin C and vitamin E stimulates the formation of so-called vitamin E and C radicals with subsequent prooxidant effects.

Finally, co-administration of statins, a confounding factor that is usually overlooked, can normalize circulating levels of vitamin E, making its administration unnecessary. Thus, rather than discarding the oxidative stress hypothesis, evidence suggests that we need more hypothesis-driven and rigorous clinical trial designs, guided by a deeper understanding of the complex physiology of ROS.

Future research will have to develop newer antioxidant compounds, more specific, with a more favourable pharmacodynamic profile or ancillary effects, or impacting systemic and tissue oxidative stress through different mechanisms.

The essentially neutral results of these interventional studies discouraged the use of antioxidant vitamin supplementation for the prevention of cardiovascular diseases, whereas the recommendation of a healthy diet, rich in fruits and vegetables and whole brain foods, is still standing.

polyphenols, a group comprising about different molecules, among which flavonoids are the most studied family. Polyphenols are potent antioxidants abundant in vegetables and particularly in derived products such as chocolate, tea, and wine. Benefits from polyphenol-rich foods and beverages are likely to arise from multiple pathways, and the antioxidant power appears to be only one of these.

First of all, it remains unclear how potent are the antioxidant properties of polyphenols and which molecules in this class are the most potent ones.
: Oxidative stress and cardiovascular diseases

Oxidative Stress in Cardiovascular Diseases	GSHPx also removes other hydroperoxides generated by free radical reactions [17]. Peroxisome proliferator-activated receptors PPARs are nuclear hormone receptors that largely modulate glucose and fatty acid metabolism and have been implicated in diabetic cardiomyopathy. Junior RF, Dabkowski ER, Shekar KC, O Connell KA, Hecker PA, Murphy MP MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload. C Redox modification of sodium—calcium exchange activity in cardiac sarcolemmal vesicles J Biol Chem Metabolic responses to reductive stress.
Author Information	Nat Clin Pract Cardiovasc Med. Laufs U, Wassmann S, Czech T, Munzel T, Eisenhauer M, Bohm M, et al. Physical inactivity increases oxidative stress, endothelial dysfunction, and atherosclerosis. Prasad DS, Das BC. Physical inactivity: a cardiovascular risk factor. Indian J Med Sci. Warburton DE, Nicol CW, Bredin SS. Health benefits of physical activity: the evidence. Pedersen BK. The diseasome of physical inactivity—and the role of myokines in muscle—fat cross talk. J Physiol. Sallam N, Laher I. Exercise modulates oxidative stress and inflammation in aging and cardiovascular diseases. Myers J, Kokkinos P, Nyelin E. Physical activity, cardiorespiratory fitness, and the metabolic syndrome. Kawamura T, Muraoka I. Exercise-induced oxidative stress and the effects of antioxidant intake from a physiological viewpoint. Fisher-Wellman K, Bloomer RJ. Acute exercise and oxidative stress: a 30 year history. Dyn Med. Goto C, Higashi Y, Kimura M, Noma K, Hara K, Nakagawa K, et al. Effect of different intensities of exercise on endothelium-dependent vasodilation in humans: role of endothelium-dependent nitric oxide and oxidative stress. Forstermann U, Munzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Tonelli AR, Haserodt S, Aytekin M, Dweik RA. Nitric oxide deficiency in pulmonary hypertension: pathobiology and implications for therapy. Pulm Circ. Hu Y, Chi L, Kuebler WM, Goldenberg NM. Perivascular inflammation in pulmonary arterial hypertension. Ntiloudi D, Qanud K, Tomaio JN, Giannakoulas G, Al-Abed Y, Zanos S. Pulmonary arterial hypertension: the case for a bioelectronic treatment. Bioelectron Med. Kenney MJ, Ganta CK. Autonomic nervous system and immune system interactions. Compr Physiol. Netea MG, Dominguez-Andres J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, et al. Defining trained immunity and its role in health and disease. Nat Rev Immunol. Elkon K, Casali P. Nature and functions of autoantibodies. Nat Clin Pract Rheumatol. Mathai SC, Hassoun PM. Pulmonary arterial hypertension associated with systemic sclerosis. Expert Rev Respir Med. Li C, Liu P, Song R, Zhang Y, Lei S, Wu S. Immune cells and autoantibodies in pulmonary arterial hypertension. Acta Biochim Biophys Sin. Barbera JA, Peinado VI, Santos S. Pulmonary hypertension in chronic obstructive pulmonary disease. Eur Respir J. Sin DD, Man SF. Chronic obstructive pulmonary disease as a risk factor for cardiovascular morbidity and mortality. Proc Am Thorac Soc. Bhatt SP, Dransfield MT. Chronic obstructive pulmonary disease and cardiovascular disease. Transl Res. Galesanu RG, Bernard S, Marquis K, Lacasse Y, Poirier P, Bourbeau J, et al. Obesity in chronic obstructive pulmonary disease: is fatter really better? Can Respir J. Whitehead A, Krause FN, Moran A, MacCannell ADV, Scragg JL, McNally BD, et al. Kruger MJ, Davies N, Myburgh KH, Lecour S Proanthocyanidins, anthocyanins and cardiovascular diseases. Int Food Res J — Kukongviriyapan U, Sompamit K, Pannangpetch P, Kukongviriyapan V, Donpunha W Preventive and therapeutic effects of quercetin on lipopolysaccharide-induced oxidative stress and vascular dysfunction in mice. Can J Physiol Pharmacol 90 10 — Kung JT, Colognori D, Lee JT Long noncoding RNAs: past, present, and future. Kunutsor SK, Spee JM, Kieneker LM, Gansevoort RT, Dullaart RPF, Voerman AJ, Touw DJ, Bakker SJL Self-reported smoking, urine cotinine, and risk of cardiovascular disease: findings from the PREVEND Prevention of Renal and Vascular End-Stage Disease Prospective Cohort Study. J Am Heart Assoc 7 10 :e Kuo CF, See LC, Yu KH, Chou IJ, Chiou MJ, Luo SF Significance of serum uric acid levels on the risk of all-cause and cardiovascular mortality. Rheumatology Oxford 52 1 — Kura B, Szeiffova Bacova B, Kalocayova B, Sykora M, Slezak J Oxidative stress-responsive microRNAs in heart injury. Int J Mol Sci 21 1 Kwekkeboom RF, Lei Z, Doevendans PA, Musters RJ, Sluijter JP Targeted delivery of miRNA therapeutics for cardiovascular diseases: opportunities and challenges. Clin Sci Lond 6 — Lassègue B, San Martín A, Griendling KK Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res 10 — Lee R, Margaritis M, Channon KM, Antoniades C Evaluating oxidative stress in human cardiovascular disease: methodological aspects and considerations. Curr Med Chem 19 16 — Lee JH, Guo Z, Myler LR, Zheng S, Paull TT Direct activation of ATM by resveratrol under oxidizing conditions. PLoS One 9 6 :e Lee PY, Chin SF, Low TY, Jamal R Probing the colorectal cancer proteome for biomarkers: current status and perspectives. J Proteome — Leopold JA Antioxidants and coronary artery disease: from pathophysiology to preventive therapy. Coron Artery Dis 26 2 — Leufkens AM, van Duijnhoven FJ, Woudt SH, Siersema PD, Jenab M, Jansen EH, Pischon T, Tjønneland A, Olsen A, Overvad K, Boutron-Ruault MC, Clavel-Chapelon F, Morois S, Palli D, Pala V, Tumino R, Vineis P, Panico S, Kaaks R, Lukanova A, Boeing H, Aleksandrova K, Trichopoulou A, Trichopoulos D, Dilis V, Peeters PH, Skeie G, González CA, Argüelles M, Sánchez MJ, Dorronsoro M, Huerta JM, Ardanaz E, Hallmans G, Palmqvist R, Khaw KT, Wareham N, Allen NE, Crowe FL, Fedirko V, Norat T, Riboli E, Bueno-de-Mesquita HB Biomarkers of oxidative stress and risk of developing colorectal cancer: a cohort-nested case-control study in the European Prospective Investigation Into Cancer and Nutrition. Am J Epidemiol 7 — Li L, Zhang HN, Chen HZ, Gao P, Zhu LH, Li HL, Lv X, Zhang QJ, Zhang R, Wang Z, She ZG, Zhang R, Wei YS, Du GH, Liu DP, Liang CC SIRT1 acts as a modulator of neointima formation following vascular injury in mice. Li Y, Chen X, Li P, Xiao Q, Hou D, Kong X CD47 antibody suppresses isoproterenol-induced cardiac hypertrophy through activation of autophagy. Am J Transl Res 12 9 — Lichtman JH, Froelicher ES, Blumenthal JA, Carney RM, Doering LV, Frasure-Smith N, Freedland KE, Jaffe AS, Leifheit-Limson EC, Sheps DS, Vaccarino V, Wulsin L American Heart Association Statistics Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association. Circulation 25; 12 Libby P, Okamoto Y, Rocha VZ, Folco E Inflammation in atherosclerosis: transition from theory to practice. Circ J 74 2 — Libby P, Ridker PM, Hansson GK Progress and challenges in translating the biology of atherosclerosis. Nature — Lim CSH, Lim SL Ferric reducing capacity versus ferric reducing antioxidant power for measuring total antioxidant capacity. Lab Med — Liu M, Li X, Lu L, Cao Y, Sun R, Chen S, Zhang P Cardiovascular disease and its relationship with chronic kidney disease. Eur Rev Med Pharmacol Sci — Liu D, Liu L, Song Z, Hu Z, Liu J, Hou D a Genetic variations of oxidative stress related genes ALOX5, ALOX5AP and MPO modulate ischemic stroke susceptibility through main effects and epistatic interactions in a Chinese population. Cell Physiol Biochem 43 4 — Liu H, Xu Z, Sun C, Gu D, Teng X, Zhao Y, Zheng Z b A variant in COX-2 gene is associated with left main coronary artery disease and clinical outcomes of coronary artery bypass grafting. Lobo V, Patil A, Phatak A, Chandra N Free radicals, antioxidants and functional foods: impact on human health. Pharmacogn Rev 4 8 — Loperena R, Harrison DG Oxidative stress and hypertensive diseases. Med Clin N Am 1 — Lowe F Biomarkers of oxidative stress. Syst Biol Free Radic Antioxid — Lu H, Cassis LA, Kooi CW, Daugherty A Structure and functions of angiotensinogen. Hypertens Res 39 7 — Lüersen K, Schmelzer C, Boesch-Saadatmandi C, Kohl C, Rimbach G, Döring F Paraoxonase 1 polymorphism QR affects the pro-inflammatory cytokine TNF-alpha in healthy males. BMC Res Notes Lyngdoh T, Marques-Vidal P, Paccaud F, Preisig M, Waeber G, Bochud M, Vollenweider P Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based Colaus study. PLoS One 6 5 :e Ma Q Transcriptional responses to oxidative stress: pathological and toxicological implications. Pharmacol Ther 3 — Ma Y, Peng D, Liu C, Huang C, Luo J Serum high concentrations of homocysteine and low levels of folic acid and vitamin B 12 are significantly correlated with the categories of coronary artery diseases. BMC Cardiovasc Disord 17 1 Mangge H, Weghuber D, Prassl R, Haara A, Schnedl W, Postolache TT, Fuchs D The role of vitamin D in atherosclerosis inflammation revisited: more a bystander than a player? Curr Vasc Pharmacol 13 3 — Maron BA, Tang SS, Loscalzo J S-nitrosothiols and the S-nitrosoproteome of the cardiovascular system. Antioxid Redox Signal 18 3 — Martínez GJ, Celermajer DS, Patel S The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation. Martín-Timón I, Sevillano-Collantes C, Segura-Galindo A, Del Cañizo-Gómez FJ Type 2 diabetes and cardiovascular disease: have all risk factors the same strength? World J Diabetes 5 4 — Mazaheri M, Karimian M, Behjati M, Raygan F, Hosseinzadeh CA Nov Association analysis of rs and rs transitions in p22phox gene with coronary artery disease: a case-control study and a computational analysis. Ir J Med Sci 4 — Mazidi M, Toth PP, Banach M C-reactive protein is associated with prevalence of the metabolic syndrome, hypertension, and diabetes mellitus in US adults. McCullough ML, Peterson JJ, Patel R, Jacques PF, Shah R, Dwyer JT Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. Am J Clin Nutr 95 2 — Meghatria F, Belhamiti O Predictive model for the risk of cardiovascular disease and type 2 diabetes in obese people. Chaos, Solitons Fractals Mehta MM, Weinberg SE, Chandel NS Mitochondrial control of immunity: beyond ATP. Nat Rev Immunol 17 10 — Meneses MJ, Silvestre R, Sousa-Lima I, Macedo MP Paraoxonase-1 as a regulator of glucose and lipid homeostasis: impact on the onset and progression of metabolic disorders. Int J Mol Sci 20 16 Merry TL, Ristow M Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training? J Physiol 18 — Messner B, Bernhard D Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol 34 3 — Meydani SN, Das SK, Pieper CF, Lewis MR, Klein S, Dixit VD, Gupta AK, Villareal DT, Bhapkar M, Huang M, Fuss PJ, Roberts SB, Holloszy JO, Fontana L Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans. Aging Albany NY 8 7 — Milagro FI, Mansego ML, De Miguel C, Martínez JA Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives. Mol Asp Med 34 4 — Mishra AK, Driessen NN, Appelmelk BJ, Besra GS Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host-pathogen interaction. FEMS Microbiol Rev 35 6 — Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 20 7 — Montezano AC, Touyz RM Reactive oxygen species, vascular Noxs, and hypertension: focus on translational and clinical research. Antioxid Redox Signal 20 1 — Montezano AC, Dulak-Lis M, Tsiropoulou S, Harvey A, Briones AM, Touyz RM Oxidative stress and human hypertension: vascular mechanisms, biomarkers, and novel therapies. Can J Cardiol 31 5 — Morrison D, Hughes J, Della Gatta PA, Mason S, Lamon S, Russell AP, Wadley GD Vitamin C and E supplementation prevents some of the cellular adaptations to endurance-training in humans. Most J, Tosti V, Redman LM, Fontana L Calorie restriction in humans: an update. Ageing Res Rev — Mozaffarian D, Wu JH Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol 58 20 — Mudau M, Genis A, Lochner A, Strijdom H Endothelial dysfunction: the early predictor of atherosclerosis. Cardiovasc J Afr 23 4 — Murphy RB, Tommasi S, Lewis BC, Mangoni AA Inhibitors of the hydrolytic enzyme dimethylarginine dimethylaminohydrolase DDAH : discovery, synthesis and development. Molecules 21 5 Nakamura K, Fuster JJ, Walsh K Adipokines: a link between obesity and cardiovascular disease. J Cardiol 63 4 — Nardinocchi L, Pantisano V, Puca R, Porru M, Aiello A, Grasselli A, Leonetti C, Safran M, Rechavi G, Givol D, Farsetti A, D'Orazi G Zinc downregulates HIF-1α and inhibits its activity in tumor cells in vitro and in vivo. PLoS One 5 12 :e Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR, CANVAS Program Collaborative Group Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 7 — Neri M, Fineschi V, Di Paolo M, Pomara C, Riezzo I, Turillazzi E, Cerretani D Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction. Curr Vasc Pharmacol 13 1 — Neves AL, Mohammedi K, Emery N, Roussel R, Fumeron F, Marre M, Velho G Allelic variations in superoxide dismutase-1 SOD1 gene and renal and cardiovascular morbidity and mortality in type 2 diabetic subjects. Mol Genet Metab 3 — Nimse SB, Pal D Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv — Nocella C, Cammisotto V, Pigozzi F, Borrione P, Fossati C, D'Amico A, Cangemi R, Peruzzi M, Gobbi G, Ettorre E, Frati G, Cavarretta E, Carnevale R, SMiLe Group Impairment between oxidant and antioxidant systems: short- and long-term implications for athletes' health. Nordestgaard BG, Varbo A Triglycerides and cardiovascular disease. Lancet — Nozik-Grayck E, Woods C, Stearman RS, Venkataraman S, Ferguson BS, Swain K, Bowler RP, Geraci MW, Ihida-Stansbury K, Stenmark KR, McKinsey TA, Domann FE Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension. Am J Phys Lung Cell Mol Phys 1 :L—L Nuhu F, Bhandari S Oxidative stress and cardiovascular complications in chronic kidney disease, the impact of anaemia. Pharmaceuticals Basel 11 4 Nuhu F, Seymour AM, Bhandari S Impact of intravenous iron on oxidative stress and mitochondrial function in experimental chronic kidney disease. Antioxidants Basel 8 10 Oelze M, Kröller-Schön S, Welschof P, Jansen T, Hausding M, Mikhed Y, Stamm P, Mader M, Zinßius E, Agdauletova S, Gottschlich A, Steven S, Schulz E, Bottari SP, Mayoux E, Münzel T, Daiber A The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity. PLoS One 9 11 :e Oliveira-Paula GH, Lacchini R, Tanus-Santos JE Clinical and pharmacogenetic impact of endothelial nitric oxide synthase polymorphisms on cardiovascular diseases. Nitric Oxide — Oni-Orisan A, Deng Y, Schuck RN, Theken KN, Edin ML, Lih FB, Molnar K, DeGraff L, Tomer KB, Zeldin DC, Lee CR Dual modulation of cyclooxygenase and CYP epoxygenase metabolism and acute vascular inflammation in mice. Prostaglandins Other Lipid Mediat — Ouchi N, Parker JL, Lugus JJ, Walsh K Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11 2 — Parthasarathy S, Raghavamenon A, Garelnabi MO, Santanam N Oxidized low-density lipoprotein. Methods Mol Biol — Pelliccia F, Kaski JC, Crea F, Camici PG Pathophysiology of Takotsubo Syndrome. Circulation 24 — Peng JR, Lu TT, Chang HT, Ge X, Huang B, Li WM Elevated levels of plasma superoxide dismutases 1 and 2 in patients with coronary artery disease. Peoples JN, Saraf A, Ghazal N, Pham TT, Kwong JQ Mitochondrial dysfunction and oxidative stress in heart disease. Exp Mol Med 51 12 :1— Peterson JJ, Dwyer JT, Jacques PF, McCullough ML Associations between flavonoids and cardiovascular disease incidence or mortality in European and US populations. Nutr Rev 70 9 — Pisani A, Riccio E, Sabbatini M, Andreucci M, Del Rio A, Visciano B Effect of oral liposomal iron versus intravenous iron for treatment of iron deficiency anaemia in CKD patients: a randomized trial. Nephrol Dial Transplant 30 4 — Pompeani N, Rybalka E, Latchman H, Murphy RM, Croft K, Hayes A Skeletal muscle atrophy in sedentary Zucker obese rats is not caused by calpain-mediated muscle damage or lipid peroxidation induced by oxidative stress. J Negat Results Biomed Ponnuswamy P, Schröttle A, Ostermeier E, Grüner S, Huang PL, Ertl G, Hoffmann U, Nieswandt B, Kuhlencordt PJ eNOS protects from atherosclerosis despite relevant superoxide production by the enzyme in apoE mice. PLoS One 7 1 :e Pourvali K, Abbasi M, Mottaghi A Role of superoxide dismutase 2 gene Ala16Val polymorphism and total antioxidant capacity in diabetes and its complications. Avicenna J Med Biotechnol 8 2 — Powers SK, Smuder AJ, Kavazis AN, Hudson MB Experimental guidelines for studies designed to investigate the impact of antioxidant supplementation on exercise performance. Int J Sport Nutr Exerc Metab 20 1 :2— Prats M, Font R, García C, Muñoz-Cortés M, Cabré C, Jariod M, Romeu M, Giralt M, Martinez-Vea A Oxidative stress markers in predicting response to treatment with ferric carboxymaltose in nondialysis chronic kidney disease patients. Clin Nephrol 81 6 — Prymont-Przyminska A, Zwolinska A, Sarniak A, Wlodarczyk A, Krol M, Nowak M, de Graft-Johnson J, Padula G, Bialasiewicz P, Markowski J, Rutkowski KP, Nowak D Consumption of strawberries on a daily basis increases the non-urate 2,2-diphenylpicryl-hydrazyl DPPH radical scavenging activity of fasting plasma in healthy subjects. J Clin Biochem Nutr 55 1 — Pu LN, Zhao Z, Zhang YT Investigation on cardiovascular risk prediction using genetic information. IEEE Trans Inf Technol Biomed 16 5 — Puddu P, Puddu GM, Cravero E, Vizioli L, Muscari A Relationships among hyperuricemia, endothelial dysfunction and cardiovascular disease: molecular mechanisms and clinical implications. J Cardiol 59 3 — Purushothaman S, Renuka Nair R, Harikrishnan VS, Fernandez AC Temporal relation of cardiac hypertrophy, oxidative stress, and fatty acid metabolism in spontaneously hypertensive rat. Mol Cell Biochem — Radak Z, Torma F, Berkes I, Goto S, Mimura T, Posa A, Balogh L, Boldogh I, Suzuki K, Higuchi M, Koltai E Exercise effects on physiological function during aging. Rai H, Parveen F, Kumar S, Kapoor A, Sinha N Association of endothelial nitric oxide synthase gene polymorphisms with coronary artery disease: an updated meta-analysis and systematic review. Ramprasath T, Murugan PS, Kalaiarasan E, Gomathi P, Rathinavel A, Selvam GS Genetic association of Glutathione peroxidase-1 GPx-1 and NAD P H:Quinone Oxidoreductase 1 NQO1 variants and their association of CAD in patients with type-2 diabetes. Rao K, Sethi K, Ischia J, Gibson L, Galea L, Xiao L, Yim M, Chang M, Papa N, Bolton D, Shulkes A, Baldwin GS, Patel O Protective effect of zinc preconditioning against renal ischemia reperfusion injury is dose dependent. PLoS One 12 7 :e Rastogi A, Bhansali A SGLT2 inhibitors through the windows of EMPA-REG and CANVAS trials: a review. Diabetes Ther 8 6 — Ravipati AS, Zhang L, Koyyalamudi SR, Jeong SC, Reddy N, Bartlett J, Smith PT, Shanmugam K, Münch G, Wu MJ, Satyanarayanan M, Vysetti B Antioxidant and anti-inflammatory activities of selected Chinese medicinal plants and their relation with antioxidant content. BMC Complement Altern Med Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49 11 — Ricciotti E, FitzGerald GA Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31 5 — Richter EA, Hargreaves M Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev 93 3 — Rifkin SB, Shrubsole MJ, Cai Q, Smalley WE, Ness RM, Swift LL, Milne G, Zheng W, Murff HJ Differences in erythrocyte phospholipid membrane long-chain polyunsaturated fatty acids and the prevalence of fatty acid desaturase genotype among African Americans and European Americans. Prostaglandins Leukot Essent Fat Acids Rizzi F, Conti C, Dogliotti E, Terranegra A, Salvi E, Braga D, Ricca F, Lupoli S, Mingione A, Pivari F, Brasacchio C, Barcella M, Chittani M, D'Avila F, Turiel M, Lazzaroni M, Soldati L, Cusi D, Barlassina C Interaction between polyphenols intake and PON1 gene variants on markers of cardiovascular disease: a nutrigenetic observational study. J Transl Med 14 1 Rochette L, Zeller M, Cottin Y, Vergely C Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta 9 — Ros E Health benefits of nut consumption. Rostoff P, Szczeklik W, Piwowarska W, Konduracka E, Sanak M, Nessler J Association of common cyclooxygenase-2 COX-2 gene polymorphisms with clinical and angiographic characteristics of patients with coronary artery disease. Przegl Lek — Roy A, Rawal I, Jabbour S, Prabhakaran D Tobacco and cardiovascular disease: a summary of evidence. In: Cardiovascular, Respiratory, and Related Disorders. Rubio CP, Hernández-Ruiz J, Martinez-Subiela S, Tvarijonaviciute A, Ceron JJ Spectrophotometric assays for total antioxidant capacity TAC in dog serum: an update. BMC Vet Res 12 1 Rückert IM, Schunk M, Holle R, Schipf S, Völzke H, Kluttig A, Greiser KH, Berger K, Müller G, Ellert U, Neuhauser H, Rathmann W, Tamayo T, Moebus S, Andrich S, Meisinger C Blood pressure and lipid management fall far short in persons with type 2 diabetes: results from the DIAB-CORE Consortium including six German population-based studies. Cardiovasc Diabetol Ruggenenti P, Abbate M, Ruggiero B, Rota S, Trillini M, Aparicio C, Parvanova A, Petrov Iliev I, Pisanu G, Perna A, Russo A, Diadei O, Martinetti D, Cannata A, Carrara F, Ferrari S, Stucchi N, Remuzzi G, Fontana L, C. Study Group Renal and systemic effects of calorie restriction in patients with type 2 diabetes with abdominal obesity: a randomized controlled trial. Rysz J, Franczyk B, Ławiński J, Gluba-Brzózka A Oxidative stress in ESRD patients on dialysis and the risk of cardiovascular diseases. Antioxidants Basel 9 11 Circulation 12 — Sakai C, Ishida M, Ohba H, Yamashita H, Uchida H, Yoshizumi M, Ishida T Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced DNA damage in vascular endothelial cells. PLoS One 12 11 :e Samaranayaka AG, Li-Chan EC Food-derived peptidic antioxidants: a review of their production, assessment, and potential applications. J Funct Foods — Samaras K, Botelho NK, Chisholm DJ, Lord RV Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity Silver Spring 18 5 — Sampieri CL, Orozco-Ortega RA Matrix metalloproteinases and tissue inhibitors of metalloproteinases in chronic kidney disease and acute kidney injury: a systematic review of the literature. Samuni Y, Goldstein S, Dean OM, Berk M The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta 8 — Santillo M, Colantuoni A, Mondola P, Guida B, Damiano S NOX signaling in molecular cardiovascular mechanisms involved in the blood pressure homeostasis. Sasser JM, Cunningham MW Jr, Baylis C Serelaxin reduces oxidative stress and asymmetric dimethylarginine in angiotensin II-induced hypertension. Am J Phys Renal Phys 12 :F—F Scheepers LE, Wei FF, Stolarz-Skrzypek K, Malyutina S, Tikhonoff V, Thijs L, Salvi E, Barlassina C, Filipovský J, Casiglia E, Nikitin Y, Kawecka-Jaszcz K, Manunta P, Cusi D, Boonen A, Staessen JA, Arts IC Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study. J Hypertens 34 11 — Seals DR, Kaplon RE, Gioscia-Ryan RA, LaRocca TJ You're only as old as your arteries: translational strategies for preserving vascular endothelial function with aging. Physiology Bethesda 29 4 — Semple DJ, Bhandari S, Seymour AM Uremic cardiomyopathy is characterized by loss of the cardioprotective effects of insulin. Am J Phys Renal Phys 9 :F—F Sena LA, Chandel NS Physiological roles of mitochondrial reactive oxygen species. Mol Cell 48 2 — Sena CM, Pereira AM, Seiça R Endothelial dysfunction — a major mediator of diabetic vascular disease. Biochim Biophys Acta 12 — Senoner T, Dichtl W Oxidative stress in cardiovascular diseases: still a therapeutic target? Shadel GS, Horvath TL Mitochondrial ROS signaling in organismal homeostasis. Sheehan AL, Carrell S, Johnson B, Stanic B, Banfi B, Miller FJ Jr Role for Nox1 NADPH oxidase in atherosclerosis. Shin SJ, Chung S, Kim SJ, Lee EM, Yoo YH, Kim JW, Ahn YB, Kim ES, Moon SD, Kim MJ, Ko SH Effect of sodium-glucose co-transporter 2 inhibitor, Dapagliflozin, on renal renin-angiotensin system in an animal model of type 2 diabetes. M Ghai G Myocardial alterations due to free radical generation Am J Physiol H H Gupta M Singal P. K Time course of structure, function and metabolic changes due to an exogenous source of oxygen metabolites in rat heart Can J Physiol Pharmacol 67 Ytrehus K Myklebut R Mjos O. D Influence of oxygen radicals generated by xanthine oxidase in the isolated perfused rat heart Cardiovasc Res 20 K Beamish R. E Dhalla N. S Potential oxidative pathways of catecholamines in the formation of lipid peroxides and genesis of heart disease Adv Exp Med Biol K Kapur N Dhillon K. S Beamish R. S Role of free radicals in catecholamine-induced cardiomyopathy Can J Physiol Pharmacol 60 Meerson F. Z Disturbance of metabolism and cardiac function under the action of emotional painful stress and their prophylaxis Basic Res Cardiol 75 Hess M. L Krause S Kontos H. A Mediation of sarcoplasmic reticulum disruption in the ischemic myocardium: proposed mechanism by the interaction of hydrogen ions and oxygen-free radicals Adv Exp Med Biol K Hill M. F Ganguly N. K et al. Role of oxidative stress in heart failure subsequent to myocardial infarction Linformation Cardiologique 20 Weiss S. J Oxygen, ischemia and inflammation Acta Physiol Scand Suppl. K Higher antioxidative capacity during a chronic stable heart hypertrophy Circ Res 64 Kanter M. M Hamlin R. L Unverferth D. V Davis H. W Merola A. J Effect of exercise training on antioxidant enzymes and cardiotoxicity of doxorubicin J Appl Physiol 59 Kramer J. H Mak I. T Weglicki W. B Differential sensitivity of canine cardiac sarcolemmal and microsomal enzymes to inhibition by free radical induced lipid peroxidation Circ Res 55 Reeves J. P Bailey C. A Hale C. C Redox modification of sodium—calcium exchange activity in cardiac sarcolemmal vesicles J Biol Chem Kaneko M Singal P. K Dhalla N. Dixon I. M Kaneko M Hata T Panagia V Dhalla N. Arora R. C Hess M. L Effect of reduced oxygen intermediates on sarcolemmal muscarinic receptors from canine heart Biochem Biophys Res Commun Guarnieri C, Ceconi C, Muscari C, Flamigni F. Influence of oxygen radicals on heart metabolism. In: Caldarera CM, Harris P, editors. Advantages in studies on heart metabolism. Bologna: CLUEB, — Kako K. Paradies G Ruggiere F. M Petrosillo G Quagliariello E Peroxidative damage to cardiac mitochondria: cytochrome oxidase and cardiolipin alterations FEBS Lett Ceconi C Curello S Albertini A Ferrari R Effect of lipid peroxidation on heart mitochondria oxygen consuming and calcium transporting capacities Mol Cell Biochem 81 Nohl H Breuinger V Hegner D Influence of mitochondrial radical formation on energy linked respiration Eur J Biochem 90 Mickelson J. K Simpson P. J Jacson C. V Lucchesi B. R Protection of myocardial function and coronary vasculature by streptokinase J Cardiovasc Pharmacol 12 Kirshenbaum L. A Thomas T. P Randhawa A. K Singal P. K Time-course of cardiac myocyte injury due to oxidative stress Mol Cell Biochem 25 Vaage J Antonelli M Bufi M Irtun O et al. Exogenous reactive oxygen species deplete the isolated rat heart of antioxidants Free Radic Biol Med 22 85 Dhaliwal H Kirshenbaum L. A Randhawa A. K Correlation between antioxidant changes during hypoxia and recovery on reoxygenation Am J Physiol H H Ferrari R Ceconi C Curello S et al. Oxygen-mediated myocardial damage during ischemia and reperfusion: role of the cellular defenses against oxygen toxicity J Mol Cell Cardiol 17 Guarnieri C Flamegini E Calderera C. M Role of oxygen in cellular damage induced by reoxygenation of hypoxic heart J Mol Cell Cardiol 12 A Singal P. K Antioxidant changes in heart hypertrophy: significance during hypoxia reoxygenation injury Can J Physiol Pharmacol 70 Jolly S. R Kane W. J Bailie M. B Abrams G. D Lucchesi B. R Canine myocardial reperfusion injury: its reduction by the combined administration of superoxide dismutase and catalase Circ Res 54 Przyklenk K Kloner R. Ferrari R Agnoletti L Comini L et al. Oxidative stress during myocardial ischemia and heart failure Eur Heart J 19 B2 B Yasmin W Strynadka K. D Schulz R Generation of peroxynitrite contributes to ischemia—reperfusion-injury in isolated rat hearts Cardiovasc Res 33 Bolli R Patel B. S Jeroudi M. O Lai E. K McCay P. Doroshow J. H Effect of anthracycline antibiotics on oxygen radical formation in rat heart Cancer Res 43 Siveski-Iliskovic N Kaul N Singal P. K Probucol promotes endogenous antioxidants and provides protection against adriamycin-induced cardiomyopathy in rats Circulation 89 Siveski-Iliskovic N Hill M Chow D. K Probucol protects against adriamycin cardiomyopathy without interfering with its antitumor effect Circulation 91 10 K Iliskovic N Li T Kumar D Adriamycin cardiomyopathy: pathophysiology and prevention FASEB J 11 Singal PK, Iliskovic N. Adriamycin cardiomyopathy. N Eng J Med in press. Myers C. E McGuire W. P Liss R. H et al. Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response Science 19 K Tong J Vitamin E deficiency accentuates adriamycin-induced cardiomyopathy and cell surface changes Mol Cell Biochem 84 Jequier E Perret C Urinary excretion of catecholamines and their main metabolites after myocardial infarction: relationship to the clinical syndrome Eur J Clin Invest 1 77 Valori C Thomas M Shillingford J Free noradrenaline and adrenaline excretion in relation to clinical syndromes following myocardial infarction Am J Cardiol 20 Francis G. S Goldsmith S. R Cohn J. N Relationship of exercise capacity to resting left ventricular performance and basal plasma norepinephrine levels in patients with congestive heart failure Am Heart J A Gupta M Thomas T. P Singal P. K Antioxidant protection against adrenaline-induced arrhythmias in rats with chronic heart hypertrophy Can J Cardiol 6 71 Barrington P. L Meier C. F Weglicki B Abnormal electrical activity induced by free radical generating systems in neutrophil NADPH oxidase FEBS Lett Beresewicz A Horackova M Alterations in electrical and contractile behaviour of isolated cardiomyocytes by hydrogen peroxide: possible ionic mechanisms J Mol Cell Cardiol 23 Bernier M Manning A. S Hearse D. J Reperfusion arrhythmias: dose-related protection by anti-free radical interventions Am J Physiol 5 pt 2 H H K Kirshenbaum L. A A relative deficit in antioxidant reserve may contribute in cardiac failure Can J Cardiol 6 47 Randhawa A. K Pressure overload induced cardiac hypertrophy with and without dilation J Am Coll Cardiol 20 Dhalla A. K Antioxidant changes in hypertrophied and failing guinea pig hearts Am J Physiol Heart and Circ. F Singal P. K Role of oxidative stress in transition of hypertrophy to heart failure J Am Coll Cardiol 28 Hill M. K Antioxidant and oxidative stress changes during heart failure subsequent to myocardial infarction in rats Am J Pathol K Right and left myocardial antioxidant responses during heart failure subsequent to myocardial infarction Circulation 96 Khaper N Singal P. K Effects of afterload reducing drugs on the pathogenesis of antioxidant changes and congestive heart failure in rats J Am Coll Cardiol 29 Packer L Protective role of vitamin E in biological systems Am J Clin Nutr 53 Axford-Gatley R. A Wilson G. J Reduction of experimental myocardial infarct size by oral administration of alpha tocopherol Cardiovasc Res 25 89 Mickle D. D Myocardial salvage with trolox and ascorbic acid for an acute evolving infarction Ann Thorac Surg 47 Massey K. D Burton K. P Alpha tocopherol attenuates myocardial membrane-related alterations resulting from ischemia and reperfusion Am J Physiol H H Klein H. H Pich S Lindert S et al. Combined treatment with vitamin E and C in experimental myocardial infarction in pigs Am Heart J Saraste A Pulkki K Kallajoki M et al. Apoptosis in human acute myocardial infarction Circulation 95 Narula J Haider N Virmani R et al. Programmed myocyte death in end-stage heart failure N Engl J Med Olivetti G Abbi R Quaini F et al. Apoptosis in the failing human heart N Engl J Med Gottlieb R. A Burleson K. O Kloner R. A Babior B. M Engler R. L Reperfusion injury induces apoptosis in rabbit cardiomyocytes J Clin Invest 94 Kajstura J Cheng W Reiss K et al. Apoptotic and necrotic myocyte cell death are independent contributing variables of infarct size in rats Lab Invest 74 86 Teiger E Dam T. Apoptosis in pressure overload-induced heart hypertrophy in the rat J Clin Invest 97 Hockenbery D. M Oltvai Z. N Yin X. L Korsmeyer S. J Bcl-2 functions in an antioxidant pathway to prevent apoptosis Cell 75 Buttke T. M Sandstrom P. A Oxidative stress as a mediator of apoptosis Immunol Today 15 7
Oxidative Stress in Cardiovascular Diseases \| IntechOpen	Similar to conditions of unregulated ROS production, an impairment in cellular antioxidant defenses and ROS scavenging can also lead to cardiac dysfunction 7 , 8 , 9 , 10 , This mechanism reduces MDA levels and ameliorates doxorubicin-induced cardiomyopathy in rats [ ]. Google Scholar. Pan S, Berk BC. Despite this importance, any derailment of NO or superoxide generation may play a pivotal role in the development and establishment of numerous cardiac and pulmonary disease conditions 4 , Kim CS, Kim YR, Naqvi A, Kumar S, Hoffman TA, Jung SB, Kumar A, Jeon BH, McNamara DM, Irani K Homocysteine promotes human endothelial cell dysfunction via site-specific epigenetic regulation of p66shc. Cell Death Dis.
Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease	Oxidative stress and antioxidative therapy in pulmonary arterial hypertension. Kattoor AJ, Goel A, Mehta JL. LOX regulation, signaling and its role in atherosclerosis. Song R, Dasgupta C, Mulder C, Zhang L. MicroRNA controls mitochondrial metabolism and protects heart function in myocardial infarction. Xiao W, Loscalzo J. Metabolic responses to reductive stress. Antioxid Redox Signal. Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biol. Villalpando-Rodriguez GE, Gibson SB. Reactive oxygen species ROS regulates different types of cell death by acting as a rheostat. Slimen IB, Najar T, Ghram A, Dabbebi H, Ben Mrad M, Abdrabbah M. Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review. Int J Hyperthermia. Article CAS PubMed Google Scholar. Vatner SF, Zhang J, Oydanich M, Berkman T, Naftalovich R, Vatner DE. Healthful aging mediated by inhibition of oxidative stress. Ageing Res Rev. Forrester SJ, Kikuchi DS, Hernandes MS, Xu Q, Griendling KK. Reactive oxygen species in metabolic and inflammatory signaling. Circ Res. Nolfi-Donegan D, Braganza A, Shiva S. Mitochondrial electron transport chain: oxidative phosphorylation, oxidant production, and methods of measurement. Zhao R-Z, Jiang S, Zhang L, Yu Z-B. Mitochondrial electron transport chain, ROS generation and uncoupling review. Int J Mol Med. Zhao S, Zang G, Zhang Y, Liu H, Wang N, Cai S, et al. Biosens Bioelectron. Mittler R. ROS are good. Trends Plant Sci. Wang Y, Hekimi S. Understanding ubiquinone. Trends Cell Biol. Hahner F, Moll F, Schröder K. NADPH oxidases in the differentiation of endothelial cells. Cardiovasc Res. Georgiou CD, Margaritis LH. Oxidative stress and NADPH oxidase: connecting electromagnetic fields, cation channels and biological effects. Int J Mole Sci. Article Google Scholar. Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: oxidative eustress. Reyhani A, McKenzie TG, Fu Q, Qiao GG. Fenton-chemistry-mediated radical polymerization. Macromol Rapid Commun. Halliwell B, Adhikary A, Dingfelder M, Dizdaroglu M. Hydroxyl radical is a significant player in oxidative DNA damage in vivo. Chem Soc Rev. Ju H-Q, Lin J-F, Tian T, Xie D, Xu R-H. NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications. Signal Transduct Target Ther. Canton M, Sánchez-Rodríguez R, Spera I, Venegas FC, Favia M, Viola A, et al. Reactive oxygen species in macrophages: sources and targets. Front Immunol. Herb M, Schramm M. Functions of ROS in macrophages and antimicrobial immunity. Szanto I. NADPH Oxidase 4 NOX4 in cancer: linking redox signals to oncogenic metabolic adaptation. Shatwell KP, Segal AW. NADPH oxidase. Int J Biochem Cell Biol. Ogboo BC, Grabovyy UV, Maini A, Scouten S, van der Vliet A, Mattevi A, et al. Architecture of the NADPH oxidase family of enzymes. Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. Article PubMed Google Scholar. Godo S, Shimokawa H. Divergent roles of endothelial nitric oxide synthases system in maintaining cardiovascular homeostasis. Free Radical Biol Med. Endothelial functions. Arterioscler Thromb Vasc Biol. Gliozzi M, Scicchitano M, Bosco F, Musolino V, Carresi C, Scarano F, et al. Modulation of nitric oxide synthases by oxidized LDLs: role in vascular inflammation and atherosclerosis development. Janaszak-Jasiecka A, Siekierzycka A, Ploska A, Dobrucki IT, Kalinowski L. Endothelial dysfunction driven by hypoxia-the influence of oxygen deficiency on NO bioavailability. Panda P, Verma HK, Lakkakula S, Merchant N, Kadir F, Rahman S, et al. Biomarkers of oxidative stress tethered to cardiovascular diseases. Bailey JD, Diotallevi M, Nicol T, McNeill E, Shaw A, Chuaiphichai S, et al. Nitric oxide modulates metabolic remodeling in inflammatory macrophages through TCA cycle regulation and itaconate accumulation. Cell Rep. Tejero J, Shiva S, Gladwin MT. Sources of vascular nitric oxide and reactive oxygen species and their regulation. Physiol Rev. Ally A, Powell I, Ally MM, Chaitoff K, Nauli SM. Role of neuronal nitric oxide synthase on cardiovascular functions in physiological and pathophysiological states. Nitric Oxide. Amodio G, Moltedo O, Faraonio R, Remondelli P. Targeting the endoplasmic reticulum unfolded protein response to counteract the oxidative stress-induced endothelial dysfunction. Chong WC, Shastri MD, Eri R. Endoplasmic reticulum stress and oxidative stress: a vicious nexus implicated in bowel disease pathophysiology. Fuhrmann DC, Brüne B. Mitochondrial composition and function under the control of hypoxia. Kampjut D, Sazanov LA. The coupling mechanism of mammalian respiratory complex I. Fiedorczuk K, Sazanov LA. Mammalian mitochondrial complex i structure and disease-causing mutations. Bezawork-Geleta A, Rohlena J, Dong L, Pacak K, Neuzil J. Mitochondrial complex II: at the crossroads. Trends Biochem Sci. Hadrava Vanova K, Kraus M, Neuzil J, Rohlena J. Mitochondrial complex II and reactive oxygen species in disease and therapy. Redox Rep. The role of the electron transport chain in immunity. Faseb J. Kadenbach B. Complex IV - the regulatory center of mitochondrial oxidative phosphorylation. Trombetti S, Cesaro E, Catapano R, Sessa R, Lo Bianco A, Izzo P, et al. Oxidative stress and ROS-mediated signaling in leukemia: novel promising perspectives to eradicate chemoresistant cells in myeloid leukemia. Sandalio LM, Romero-Puertas MC. Peroxisomes sense and respond to environmental cues by regulating ROS and RNS signalling networks. Ann Bot. Walker CL, Pomatto LCD, Tripathi DN, Davies KJA. Redox regulation of homeostasis and proteostasis in peroxisomes. Fulton DJR, Li X, Bordan Z, Haigh S, Bentley A, Chen F, et al. Reactive oxygen and nitrogen species in the development of pulmonary hypertension. Libby P, Buring JE, Badimon L, Hansson GK, Deanfield J, Bittencourt MS, et al. Nat Rev Dis Primers. Xu S, Pelisek J, Jin ZG. Atherosclerosis is an epigenetic disease. Trends Endocrinol Metab. Soehnlein O, Libby P. Targeting inflammation in atherosclerosis - from experimental insights to the clinic. Mury P, Chirico EN, Mura M, Millon A, Canet-Soulas E, Pialoux V. Oxidative stress and inflammation, key targets of atherosclerotic plaque progression and vulnerability: potential impact of physical activity. Sports Med. DeFilippis AP, Chapman AR, Mills NL, de Lemos JA, Arbab-Zadeh A, Newby LK, et al. Assessment and treatment of patients with type 2 myocardial infarction and acute nonischemic myocardial injury. Wu X, Reboll MR, Korf-Klingebiel M, Wollert KC. Angiogenesis after acute myocardial infarction. Bugger H, Pfeil K. Mitochondrial ROS in myocardial ischemia reperfusion and remodeling. Biochim Biophys Acta Mol Basis Dis. Evans CE, Cober ND, Dai Z, Stewart DJ, Zhao YY. Endothelial cells in the pathogenesis of pulmonary arterial hypertension. Eur Respir J. Fukai T, Ushio-Fukai M. Cross-talk between NADPH oxidase and mitochondria: role in ROS signaling and angiogenesis. Yu WC, Chen HY, Yang HL, Xia P, Zou CW, Sun TW, et al. Stem Cells Int. Smith TL, Oubaha M, Cagnone G, Boscher C, Kim JS, El Bakkouri Y, et al. eNOS controls angiogenic sprouting and retinal neovascularization through the regulation of endothelial cell polarity. Cell Mol Life Sci. Leo F, Suvorava T, Heuser SK, Li J, LoBue A, Barbarino F, et al. Red blood cell and endothelial eNOS independently regulate circulating nitric oxide metabolites and blood pressure. El Hadri K, Smith R, Duplus E, El Amri C. Inflammation, oxidative stress, senescence in atherosclerosis: thioredoxine-1 as an emerging therapeutic target. Kigawa Y, Miyazaki T, Lei XF, Kim-Kaneyama JR, Miyazaki A. Functional heterogeneity of nadph oxidases in atherosclerotic and aneurysmal diseases. J Atheroscler Thromb. Park K, Li Q, Lynes MD, Yokomizo H, Maddaloni E, Shinjo T, et al. Endothelial cells induced progenitors into brown fat to reduce atherosclerosis. Langbein H, Brunssen C, Hofmann A, Cimalla P, Brux M, Bornstein SR, et al. NADPH oxidase 4 protects against development of endothelial dysfunction and atherosclerosis in LDL receptor deficient mice. Chang X, Lochner A, Wang HH, Wang S, Zhu H, Ren J, et al. Coronary microvascular injury in myocardial infarction: perception and knowledge for mitochondrial quality control. Yu X, Ge L, Niu L, Lian X, Ma H, Pang L. Zhang Y, Yang Y. Mol Med Rep. Al-Botaty BM, Elkhoely A, El-Sayed EK, Ahmed AAE. Ethyl pyruvate attenuates isoproterenol-induced myocardial infarction in rats: insight to TNF-α-mediated apoptotic and necroptotic signaling interplay. Int Immunopharmacol. Yang Z, Wu QQ, Xiao Y, Duan MX, Liu C, Yuan Y, et al. Li J, Zhang Y, Li C, Xie J, Liu Y, Zhu W, et al. HSPA12B attenuates cardiac dysfunction and remodelling after myocardial infarction through an eNOS-dependent mechanism. Zhan B, Xu Z, Zhang Y, Wan K, Deng H, Wang D, et al. Biomed Pharmacother. Carnesecchi S, Deffert C, Pagano A, Garrido-Urbani S, Métrailler-Ruchonnet I, Schäppi M, et al. NADPH oxidase-1 plays a crucial role in hyperoxia-induced acute lung injury in mice. Am J Respir Crit Care Med. Hood KY, Mair KM, Harvey AP, Montezano AC, Touyz RM, MacLean MR. Serotonin signaling through the 5-HT 1B receptor and NADPH oxidase 1 in pulmonary arterial hypertension. Park JM, Do VQ, Seo YS, Kim HJ, Nam JH, Yin MZ, et al. NADPH oxidase 1 mediates acute blood pressure response to angiotensin II by contributing to calcium influx in vascular smooth muscle cells. de Jesus DS, DeVallance E, Li Y, Falabella M, Guimaraes D, Shiva S, et al. Kim YM, Kim SJ, Tatsunami R, Yamamura H, Fukai T, Ushio-Fukai M. ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF signaling and angiogenesis. Am J Physiol Cell Physiol. Jiang J, Huang K, Xu S, Garcia JGN, Wang C, Cai H. Iwata K, Ikami K, Matsuno K, Yamashita T, Shiba D, Ibi M, et al. Lee S, Paudel O, Jiang Y, Yang XR, Sham JS. Am J Respir Cell Mol Biol. Hood KY, Montezano AC, Harvey AP, Nilsen M, MacLean MR, Touyz RM. Nicotinamide adenine dinucleotide phosphate oxidase-mediated redox signaling and vascular remodeling by 16α-hydroxyestrone in human pulmonary artery cells: implications in pulmonary arterial hypertension. Song JL, Zheng SY, He RL, Gui LX, Lin MJ, Sham JSK. Serotonin and chronic hypoxic pulmonary hypertension activate a NADPH oxidase 4 and TRPM2 dependent pathway for pulmonary arterial smooth muscle cell proliferation and migration. Vascul Pharmacol. Liu R, Xu C, Zhang W, Cao Y, Ye J, Li B, et al. FUNDC1-mediated mitophagy and HIF1α activation drives pulmonary hypertension during hypoxia. Cell Death Dis. Liu Y, Nie X, Zhu J, Wang T, Li Y, Wang Q, et al. NDUFA4L2 in smooth muscle promotes vascular remodeling in hypoxic pulmonary arterial hypertension. J Cell Mol Med. Zimmer A, Teixeira RB, Constantin RL, Campos-Carraro C, Aparicio Cordero EA, Ortiz VD, et al. The progression of pulmonary arterial hypertension induced by monocrotaline is characterized by lung nitrosative and oxidative stress, and impaired pulmonary artery reactivity. Eur J Pharmacol. Marchio P, Guerra-Ojeda S, Vila JM, Aldasoro M, Victor VM, Mauricio MD. Targeting early atherosclerosis: a focus on oxidative stress and inflammation. Lee JH, Joo JH, Kim J, Lim HJ, Kim S, Curtiss L, et al. Interaction of NADPH oxidase 1 with Toll-like receptor 2 induces migration of smooth muscle cells. Ouerd S, Idris-Khodja N, Trindade M, Ferreira NS, Berillo O, Coelho SC, et al. Endothelium-restricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1. Wu JH, Zhang L, Nepliouev I, Brian L, Huang T, Snow KP, et al. Drebrin attenuates atherosclerosis by limiting smooth muscle cell transdifferentiation. Violi F, Carnevale R, Loffredo L, Pignatelli P, Gallin JI. NADPH Oxidase-2 and atherothrombosis: insight from chronic granulomatous disease. da Silva JF, Alves JV, Silva-Neto JA, Costa RM, Neves KB, Alves-Lopes R, et al. Lysophosphatidylcholine induces oxidative stress in human endothelial cells via NOX5 activation - implications in atherosclerosis. Clin Sci. Article CAS Google Scholar. Schürmann C, Rezende F, Kruse C, Yasar Y, Löwe O, Fork C, et al. The NADPH oxidase Nox4 has anti-atherosclerotic functions. Gray SP, Di Marco E, Kennedy K, Chew P, Okabe J, El-Osta A, et al. Reactive oxygen species can provide atheroprotection via NOX4-dependent inhibition of inflammation and vascular remodeling. Xiang M, Lu Y, Xin L, Gao J, Shang C, Jiang Z, et al. Role of oxidative stress in reperfusion following myocardial ischemia and its treatments. Cadenas S. ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection. Free Radic Biol Med. Matsushima S, Tsutsui H, Sadoshima J. Physiological and pathological functions of NADPH oxidases during myocardial ischemia-reperfusion. Trends Cardiovasc Med. Touyz RM, Anagnostopoulou A, Camargo LL, Rios FJ, Montezano AC. Vascular biology of superoxide-generating NADPH Oxidase 5-implications in hypertension and cardiovascular disease. Mongue-Din H, Patel AS, Looi YH, Grieve DJ, Anilkumar N, Sirker A, et al. NADPH oxidase-4 driven cardiac macrophage polarization protects against myocardial infarction-induced remodeling. JACC Basic Transl Sci. Ganji M, Nardi V, Prasad M, Jordan KL, Bois MC, Franchi F, et al. Carotid plaques from symptomatic patients are characterized by local increase in xanthine oxidase expression. Kimura Y, Tsukui D, Kono H. Uric acid in inflammation and the pathogenesis of atherosclerosis. Wang Y, Wang W, Wang N, Tall AR, Tabas I. Mitochondrial oxidative stress promotes atherosclerosis and neutrophil extracellular traps in aged mice. Salnikova D, Orekhova V, Grechko A, Starodubova A, Bezsonov E, Popkova T, et al. Mitochondrial dysfunction in vascular wall cells and its role in atherosclerosis. Wei Y, Corbalán-Campos J, Gurung R, Natarelli L, Zhu M, Exner N, et al. Dicer in macrophages prevents atherosclerosis by promoting mitochondrial oxidative metabolism. Heger J, Hirschhäuser C, Bornbaum J, Sydykov A, Dempfle A, Schneider A, et al. Costiniti V, Spera I, Menabò R, Palmieri EM, Menga A, Scarcia P, et al. Monoamine oxidase-dependent histamine catabolism accounts for post-ischemic cardiac redox imbalance and injury. Neha K, Haider MR, Pathak A, Yar MS. Medicinal prospects of antioxidants: a review. Eur J Med Chem. Flohé L, Toppo S, Orian L. The glutathione peroxidase family: discoveries and mechanism. Sharma A, Yuen D, Huet O, Pickering R, Stefanovic N, Bernatchez P, et al. Lack of glutathione peroxidase-1 facilitates a pro-inflammatory and activated vascular endothelium. Oelze M, Kröller-Schön S, Steven S, Lubos E, Doppler C, Hausding M, et al. Glutathione peroxidase-1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging. Pang P, Abbott M, Abdi M, Fucci QA, Chauhan N, Mistri M, et al. Pre-clinical model of severe glutathione peroxidase-3 deficiency and chronic kidney disease results in coronary artery thrombosis and depressed left ventricular function. Nephrol Dial Transplant. Brugaletta S, Scalone G, Dantas AP, Ortega-Paz L, Garabito M, Roqué M, et al. Endothelial function impairment in STEMI patients with out-of-hospital cardiac arrest under therapeutic hypothermia treatment. Int J Cardiol. Jelinek A, Heyder L, Daude M, Plessner M, Krippner S, Grosse R, et al. Mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis. Kitakata H, Endo J, Ikura H, Moriyama H, Shirakawa K, Katsumata Y, et al. Therapeutic targets for DOX-induced cardiomyopathy: role of apoptosis vs. Guo Z, Ran Q, Roberts LJ 2nd, Zhou L, Richardson A, Sharan C, et al. Suppression of atherogenesis by overexpression of glutathione peroxidase-4 in apolipoprotein E-deficient mice. Fan K, Huang W, Qi H, Song C, He C, Liu Y, et al. Wang Y, Branicky R, Noë A, Hekimi S. Superoxide dismutases: dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol. Sharma S, Bhattarai S, Ara H, Sun G, St Clair DK, Bhuiyan MS, et al. SOD2 deficiency in cardiomyocytes defines defective mitochondrial bioenergetics as a cause of lethal dilated cardiomyopathy. Tsai YT, Yeh HY, Chao CT, Chiang CK. Superoxide dismutase 2 SOD2 in vascular calcification: a focus on vascular smooth muscle cells, calcification pathogenesis, and therapeutic strategies. Pinto A, Immohr MB, Jahn A, Jenke A, Boeken U, Lichtenberg A, et al. The extracellular isoform of superoxide dismutase has a significant impact on cardiovascular ischaemia and reperfusion injury during cardiopulmonary bypass. Eur J Cardiothorac Surg. Li X, Lin Y, Wang S, Zhou S, Ju J, Wang X, et al. Extracellular superoxide dismutase is associated with left ventricular geometry and heart failure in patients with cardiovascular disease. J Am Heart Assoc. Caveolin-1 stabilizes ATP7A, a copper transporter for extracellular SOD, in vascular tissue to maintain endothelial function. Nozik-Grayck E, Woods C, Stearman RS, Venkataraman S, Ferguson BS, Swain K, et al. Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. Xu D, Guo H, Xu X, Lu Z, Fassett J, Hu X, et al. Exacerbated pulmonary arterial hypertension and right ventricular hypertrophy in animals with loss of function of extracellular superoxide dismutase. Hohl M, Mayr M, Lang L, Nickel AG, Barallobre-Barreiro J, Yin X, et al. Clin Exp Hypertens 40 4 — Kawabata K, Yoshioka Y, Terao J Role of intestinal microbiota in the bioavailability and physiological functions of dietary polyphenols. Molecules 24 2 Kay CD, Hooper L, Kroon PA, Rimm EB, Cassidy A Relative impact of flavonoid composition, dose and structure on vascular function: a systematic review of randomised controlled trials of flavonoid-rich food products. Mol Nutr Food Res 56 11 — Kaypee S, Sudarshan D, Shanmugam MK, Mukherjee D, Sethi G, Kundu TK Aberrant lysine acetylation in tumorigenesis: implications in the development of therapeutics. Kemp JR, Unal H, Desnoyer R, Yue H, Bhatnagar A, Karnik SS Angiotensin II-regulated microRNA p directly targets multiple components of the renin-angiotensin system. Khamis AA, Salama AF, Kenawy ME, Mohamed TM Regulation of hepatic hydroxy methyl glutarate - CoA reductase for controlling hypercholesterolemia in rats. Biomed Pharmacother — Kida Y, Goligorsky MS Sirtuins, cell senescence, and vascular aging. Can J Cardiol 32 5 — Kim CS, Kim YR, Naqvi A, Kumar S, Hoffman TA, Jung SB, Kumar A, Jeon BH, McNamara DM, Irani K Homocysteine promotes human endothelial cell dysfunction via site-specific epigenetic regulation of p66shc. Cardiovasc Res 92 3 — Kim GH, Ryan JJ, Archer SL The role of redox signaling in epigenetics and cardiovascular disease. Antioxid Redox Signal 18 15 — Kivimäki M, Steptoe A Effects of stress on the development and progression of cardiovascular disease. Nat Rev Cardiol 15 4 — Klarin D, Zhu QM, Emdin CA, Chaffin M, Horner S, BJ MM, Leed A, Weale ME, Spencer CCA, Aguet F, Segrè AV, Ardlie KG, Khera AV, Kaushik VK, Natarajan P, CARDIoGRAMplusC4D Consortium, Kathiresan S Genetic analysis in UK Biobank links insulin resistance and transendothelial migration pathways to coronary artery disease. Nat Genet 49 9 — Klaunig JE, Wang Z, Pu X, Zhou S Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol Appl Pharmacol 2 — Kleniewska P, Piechota A, Skibska B, Gorąca A The NADPH oxidase family and its inhibitors. Arch Immunol Ther Exp Warsz 60 4 — Koçak S, Harmankaya A, Erdemir E, Dündar ZD, Kesli R, Alibasic H Association of severity of coronary lesion with markers of acute infection and inflammation in patients with acute coronary syndrome. Eur J Emerg Med Koene RJ, Prizment AE, Blaes A, Konety SH Shared risk factors in cardiovascular disease and cancer. Kokkinos P, Myers J Exercise and physical activity: clinical outcomes and applications. Circulation 16 — Kowalska K, Socha E, Milnerowicz H Review: the role of paraoxonase in cardiovascular diseases. Ann Clin Lab Sci 45 2 — CAS Google Scholar. J Phys Fitness Sports Med — Kreutzer FP, Fiedler J, Thum T Non-coding RNAs: key players in cardiac disease. J Physiol 14 — Kruger MJ, Davies N, Myburgh KH, Lecour S Proanthocyanidins, anthocyanins and cardiovascular diseases. Int Food Res J — Kukongviriyapan U, Sompamit K, Pannangpetch P, Kukongviriyapan V, Donpunha W Preventive and therapeutic effects of quercetin on lipopolysaccharide-induced oxidative stress and vascular dysfunction in mice. Can J Physiol Pharmacol 90 10 — Kung JT, Colognori D, Lee JT Long noncoding RNAs: past, present, and future. Kunutsor SK, Spee JM, Kieneker LM, Gansevoort RT, Dullaart RPF, Voerman AJ, Touw DJ, Bakker SJL Self-reported smoking, urine cotinine, and risk of cardiovascular disease: findings from the PREVEND Prevention of Renal and Vascular End-Stage Disease Prospective Cohort Study. J Am Heart Assoc 7 10 :e Kuo CF, See LC, Yu KH, Chou IJ, Chiou MJ, Luo SF Significance of serum uric acid levels on the risk of all-cause and cardiovascular mortality. Rheumatology Oxford 52 1 — Kura B, Szeiffova Bacova B, Kalocayova B, Sykora M, Slezak J Oxidative stress-responsive microRNAs in heart injury. Int J Mol Sci 21 1 Kwekkeboom RF, Lei Z, Doevendans PA, Musters RJ, Sluijter JP Targeted delivery of miRNA therapeutics for cardiovascular diseases: opportunities and challenges. Clin Sci Lond 6 — Lassègue B, San Martín A, Griendling KK Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res 10 — Lee R, Margaritis M, Channon KM, Antoniades C Evaluating oxidative stress in human cardiovascular disease: methodological aspects and considerations. Curr Med Chem 19 16 — Lee JH, Guo Z, Myler LR, Zheng S, Paull TT Direct activation of ATM by resveratrol under oxidizing conditions. PLoS One 9 6 :e Lee PY, Chin SF, Low TY, Jamal R Probing the colorectal cancer proteome for biomarkers: current status and perspectives. J Proteome — Leopold JA Antioxidants and coronary artery disease: from pathophysiology to preventive therapy. Coron Artery Dis 26 2 — Leufkens AM, van Duijnhoven FJ, Woudt SH, Siersema PD, Jenab M, Jansen EH, Pischon T, Tjønneland A, Olsen A, Overvad K, Boutron-Ruault MC, Clavel-Chapelon F, Morois S, Palli D, Pala V, Tumino R, Vineis P, Panico S, Kaaks R, Lukanova A, Boeing H, Aleksandrova K, Trichopoulou A, Trichopoulos D, Dilis V, Peeters PH, Skeie G, González CA, Argüelles M, Sánchez MJ, Dorronsoro M, Huerta JM, Ardanaz E, Hallmans G, Palmqvist R, Khaw KT, Wareham N, Allen NE, Crowe FL, Fedirko V, Norat T, Riboli E, Bueno-de-Mesquita HB Biomarkers of oxidative stress and risk of developing colorectal cancer: a cohort-nested case-control study in the European Prospective Investigation Into Cancer and Nutrition. Am J Epidemiol 7 — Li L, Zhang HN, Chen HZ, Gao P, Zhu LH, Li HL, Lv X, Zhang QJ, Zhang R, Wang Z, She ZG, Zhang R, Wei YS, Du GH, Liu DP, Liang CC SIRT1 acts as a modulator of neointima formation following vascular injury in mice. Li Y, Chen X, Li P, Xiao Q, Hou D, Kong X CD47 antibody suppresses isoproterenol-induced cardiac hypertrophy through activation of autophagy. Am J Transl Res 12 9 — Lichtman JH, Froelicher ES, Blumenthal JA, Carney RM, Doering LV, Frasure-Smith N, Freedland KE, Jaffe AS, Leifheit-Limson EC, Sheps DS, Vaccarino V, Wulsin L American Heart Association Statistics Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association. Circulation 25; 12 Libby P, Okamoto Y, Rocha VZ, Folco E Inflammation in atherosclerosis: transition from theory to practice. Circ J 74 2 — Libby P, Ridker PM, Hansson GK Progress and challenges in translating the biology of atherosclerosis. Nature — Lim CSH, Lim SL Ferric reducing capacity versus ferric reducing antioxidant power for measuring total antioxidant capacity. Lab Med — Liu M, Li X, Lu L, Cao Y, Sun R, Chen S, Zhang P Cardiovascular disease and its relationship with chronic kidney disease. Eur Rev Med Pharmacol Sci — Liu D, Liu L, Song Z, Hu Z, Liu J, Hou D a Genetic variations of oxidative stress related genes ALOX5, ALOX5AP and MPO modulate ischemic stroke susceptibility through main effects and epistatic interactions in a Chinese population. Cell Physiol Biochem 43 4 — Liu H, Xu Z, Sun C, Gu D, Teng X, Zhao Y, Zheng Z b A variant in COX-2 gene is associated with left main coronary artery disease and clinical outcomes of coronary artery bypass grafting. Lobo V, Patil A, Phatak A, Chandra N Free radicals, antioxidants and functional foods: impact on human health. Pharmacogn Rev 4 8 — Loperena R, Harrison DG Oxidative stress and hypertensive diseases. Med Clin N Am 1 — Lowe F Biomarkers of oxidative stress. Syst Biol Free Radic Antioxid — Lu H, Cassis LA, Kooi CW, Daugherty A Structure and functions of angiotensinogen. Hypertens Res 39 7 — Lüersen K, Schmelzer C, Boesch-Saadatmandi C, Kohl C, Rimbach G, Döring F Paraoxonase 1 polymorphism QR affects the pro-inflammatory cytokine TNF-alpha in healthy males. BMC Res Notes Lyngdoh T, Marques-Vidal P, Paccaud F, Preisig M, Waeber G, Bochud M, Vollenweider P Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based Colaus study. PLoS One 6 5 :e Ma Q Transcriptional responses to oxidative stress: pathological and toxicological implications. Pharmacol Ther 3 — Ma Y, Peng D, Liu C, Huang C, Luo J Serum high concentrations of homocysteine and low levels of folic acid and vitamin B 12 are significantly correlated with the categories of coronary artery diseases. BMC Cardiovasc Disord 17 1 Mangge H, Weghuber D, Prassl R, Haara A, Schnedl W, Postolache TT, Fuchs D The role of vitamin D in atherosclerosis inflammation revisited: more a bystander than a player? Curr Vasc Pharmacol 13 3 — Maron BA, Tang SS, Loscalzo J S-nitrosothiols and the S-nitrosoproteome of the cardiovascular system. Antioxid Redox Signal 18 3 — Martínez GJ, Celermajer DS, Patel S The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation. Martín-Timón I, Sevillano-Collantes C, Segura-Galindo A, Del Cañizo-Gómez FJ Type 2 diabetes and cardiovascular disease: have all risk factors the same strength? World J Diabetes 5 4 — Mazaheri M, Karimian M, Behjati M, Raygan F, Hosseinzadeh CA Nov Association analysis of rs and rs transitions in p22phox gene with coronary artery disease: a case-control study and a computational analysis. Ir J Med Sci 4 — Mazidi M, Toth PP, Banach M C-reactive protein is associated with prevalence of the metabolic syndrome, hypertension, and diabetes mellitus in US adults. McCullough ML, Peterson JJ, Patel R, Jacques PF, Shah R, Dwyer JT Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. Am J Clin Nutr 95 2 — Meghatria F, Belhamiti O Predictive model for the risk of cardiovascular disease and type 2 diabetes in obese people. Chaos, Solitons Fractals Mehta MM, Weinberg SE, Chandel NS Mitochondrial control of immunity: beyond ATP. Nat Rev Immunol 17 10 — Meneses MJ, Silvestre R, Sousa-Lima I, Macedo MP Paraoxonase-1 as a regulator of glucose and lipid homeostasis: impact on the onset and progression of metabolic disorders. Int J Mol Sci 20 16 Merry TL, Ristow M Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training? J Physiol 18 — Messner B, Bernhard D Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol 34 3 — Meydani SN, Das SK, Pieper CF, Lewis MR, Klein S, Dixit VD, Gupta AK, Villareal DT, Bhapkar M, Huang M, Fuss PJ, Roberts SB, Holloszy JO, Fontana L Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans. Aging Albany NY 8 7 — Milagro FI, Mansego ML, De Miguel C, Martínez JA Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives. Mol Asp Med 34 4 — Mishra AK, Driessen NN, Appelmelk BJ, Besra GS Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host-pathogen interaction. FEMS Microbiol Rev 35 6 — Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 20 7 — Montezano AC, Touyz RM Reactive oxygen species, vascular Noxs, and hypertension: focus on translational and clinical research. Antioxid Redox Signal 20 1 — Montezano AC, Dulak-Lis M, Tsiropoulou S, Harvey A, Briones AM, Touyz RM Oxidative stress and human hypertension: vascular mechanisms, biomarkers, and novel therapies. Can J Cardiol 31 5 — Morrison D, Hughes J, Della Gatta PA, Mason S, Lamon S, Russell AP, Wadley GD Vitamin C and E supplementation prevents some of the cellular adaptations to endurance-training in humans. Most J, Tosti V, Redman LM, Fontana L Calorie restriction in humans: an update. Ageing Res Rev — Mozaffarian D, Wu JH Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol 58 20 — Mudau M, Genis A, Lochner A, Strijdom H Endothelial dysfunction: the early predictor of atherosclerosis. Cardiovasc J Afr 23 4 — Murphy RB, Tommasi S, Lewis BC, Mangoni AA Inhibitors of the hydrolytic enzyme dimethylarginine dimethylaminohydrolase DDAH : discovery, synthesis and development. Molecules 21 5 Nakamura K, Fuster JJ, Walsh K Adipokines: a link between obesity and cardiovascular disease. J Cardiol 63 4 — Nardinocchi L, Pantisano V, Puca R, Porru M, Aiello A, Grasselli A, Leonetti C, Safran M, Rechavi G, Givol D, Farsetti A, D'Orazi G Zinc downregulates HIF-1α and inhibits its activity in tumor cells in vitro and in vivo. PLoS One 5 12 :e Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR, CANVAS Program Collaborative Group Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 7 — Neri M, Fineschi V, Di Paolo M, Pomara C, Riezzo I, Turillazzi E, Cerretani D Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction. Curr Vasc Pharmacol 13 1 — Neves AL, Mohammedi K, Emery N, Roussel R, Fumeron F, Marre M, Velho G Allelic variations in superoxide dismutase-1 SOD1 gene and renal and cardiovascular morbidity and mortality in type 2 diabetic subjects. Mol Genet Metab 3 — Nimse SB, Pal D Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv — Nocella C, Cammisotto V, Pigozzi F, Borrione P, Fossati C, D'Amico A, Cangemi R, Peruzzi M, Gobbi G, Ettorre E, Frati G, Cavarretta E, Carnevale R, SMiLe Group Impairment between oxidant and antioxidant systems: short- and long-term implications for athletes' health. Nordestgaard BG, Varbo A Triglycerides and cardiovascular disease. Lancet — Nozik-Grayck E, Woods C, Stearman RS, Venkataraman S, Ferguson BS, Swain K, Bowler RP, Geraci MW, Ihida-Stansbury K, Stenmark KR, McKinsey TA, Domann FE Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension. Am J Phys Lung Cell Mol Phys 1 :L—L Nuhu F, Bhandari S Oxidative stress and cardiovascular complications in chronic kidney disease, the impact of anaemia. Pharmaceuticals Basel 11 4 Nuhu F, Seymour AM, Bhandari S Impact of intravenous iron on oxidative stress and mitochondrial function in experimental chronic kidney disease. Antioxidants Basel 8 10 Oelze M, Kröller-Schön S, Welschof P, Jansen T, Hausding M, Mikhed Y, Stamm P, Mader M, Zinßius E, Agdauletova S, Gottschlich A, Steven S, Schulz E, Bottari SP, Mayoux E, Münzel T, Daiber A The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity. PLoS One 9 11 :e Oliveira-Paula GH, Lacchini R, Tanus-Santos JE Clinical and pharmacogenetic impact of endothelial nitric oxide synthase polymorphisms on cardiovascular diseases. Nitric Oxide — Oni-Orisan A, Deng Y, Schuck RN, Theken KN, Edin ML, Lih FB, Molnar K, DeGraff L, Tomer KB, Zeldin DC, Lee CR Dual modulation of cyclooxygenase and CYP epoxygenase metabolism and acute vascular inflammation in mice. Prostaglandins Other Lipid Mediat — Ouchi N, Parker JL, Lugus JJ, Walsh K Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11 2 — Parthasarathy S, Raghavamenon A, Garelnabi MO, Santanam N Oxidized low-density lipoprotein. Methods Mol Biol — Pelliccia F, Kaski JC, Crea F, Camici PG Pathophysiology of Takotsubo Syndrome. Circulation 24 — Peng JR, Lu TT, Chang HT, Ge X, Huang B, Li WM Elevated levels of plasma superoxide dismutases 1 and 2 in patients with coronary artery disease. Peoples JN, Saraf A, Ghazal N, Pham TT, Kwong JQ Mitochondrial dysfunction and oxidative stress in heart disease. Exp Mol Med 51 12 :1— Peterson JJ, Dwyer JT, Jacques PF, McCullough ML Associations between flavonoids and cardiovascular disease incidence or mortality in European and US populations. Nutr Rev 70 9 — Pisani A, Riccio E, Sabbatini M, Andreucci M, Del Rio A, Visciano B Effect of oral liposomal iron versus intravenous iron for treatment of iron deficiency anaemia in CKD patients: a randomized trial. Nephrol Dial Transplant 30 4 — Pompeani N, Rybalka E, Latchman H, Murphy RM, Croft K, Hayes A Skeletal muscle atrophy in sedentary Zucker obese rats is not caused by calpain-mediated muscle damage or lipid peroxidation induced by oxidative stress. J Negat Results Biomed Ponnuswamy P, Schröttle A, Ostermeier E, Grüner S, Huang PL, Ertl G, Hoffmann U, Nieswandt B, Kuhlencordt PJ eNOS protects from atherosclerosis despite relevant superoxide production by the enzyme in apoE mice. PLoS One 7 1 :e Pourvali K, Abbasi M, Mottaghi A Role of superoxide dismutase 2 gene Ala16Val polymorphism and total antioxidant capacity in diabetes and its complications. Avicenna J Med Biotechnol 8 2 — Powers SK, Smuder AJ, Kavazis AN, Hudson MB Experimental guidelines for studies designed to investigate the impact of antioxidant supplementation on exercise performance. Int J Sport Nutr Exerc Metab 20 1 :2— Prats M, Font R, García C, Muñoz-Cortés M, Cabré C, Jariod M, Romeu M, Giralt M, Martinez-Vea A Oxidative stress markers in predicting response to treatment with ferric carboxymaltose in nondialysis chronic kidney disease patients. Clin Nephrol 81 6 — Prymont-Przyminska A, Zwolinska A, Sarniak A, Wlodarczyk A, Krol M, Nowak M, de Graft-Johnson J, Padula G, Bialasiewicz P, Markowski J, Rutkowski KP, Nowak D Consumption of strawberries on a daily basis increases the non-urate 2,2-diphenylpicryl-hydrazyl DPPH radical scavenging activity of fasting plasma in healthy subjects. J Clin Biochem Nutr 55 1 — Pu LN, Zhao Z, Zhang YT Investigation on cardiovascular risk prediction using genetic information. IEEE Trans Inf Technol Biomed 16 5 — Puddu P, Puddu GM, Cravero E, Vizioli L, Muscari A Relationships among hyperuricemia, endothelial dysfunction and cardiovascular disease: molecular mechanisms and clinical implications. J Cardiol 59 3 — Purushothaman S, Renuka Nair R, Harikrishnan VS, Fernandez AC Temporal relation of cardiac hypertrophy, oxidative stress, and fatty acid metabolism in spontaneously hypertensive rat. Mol Cell Biochem — Radak Z, Torma F, Berkes I, Goto S, Mimura T, Posa A, Balogh L, Boldogh I, Suzuki K, Higuchi M, Koltai E Exercise effects on physiological function during aging. Rai H, Parveen F, Kumar S, Kapoor A, Sinha N Association of endothelial nitric oxide synthase gene polymorphisms with coronary artery disease: an updated meta-analysis and systematic review. Ramprasath T, Murugan PS, Kalaiarasan E, Gomathi P, Rathinavel A, Selvam GS Genetic association of Glutathione peroxidase-1 GPx-1 and NAD P H:Quinone Oxidoreductase 1 NQO1 variants and their association of CAD in patients with type-2 diabetes. Rao K, Sethi K, Ischia J, Gibson L, Galea L, Xiao L, Yim M, Chang M, Papa N, Bolton D, Shulkes A, Baldwin GS, Patel O Protective effect of zinc preconditioning against renal ischemia reperfusion injury is dose dependent. PLoS One 12 7 :e Rastogi A, Bhansali A SGLT2 inhibitors through the windows of EMPA-REG and CANVAS trials: a review. Diabetes Ther 8 6 — Ravipati AS, Zhang L, Koyyalamudi SR, Jeong SC, Reddy N, Bartlett J, Smith PT, Shanmugam K, Münch G, Wu MJ, Satyanarayanan M, Vysetti B Antioxidant and anti-inflammatory activities of selected Chinese medicinal plants and their relation with antioxidant content. BMC Complement Altern Med Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49 11 — Ricciotti E, FitzGerald GA Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31 5 — Richter EA, Hargreaves M Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev 93 3 — Rifkin SB, Shrubsole MJ, Cai Q, Smalley WE, Ness RM, Swift LL, Milne G, Zheng W, Murff HJ Differences in erythrocyte phospholipid membrane long-chain polyunsaturated fatty acids and the prevalence of fatty acid desaturase genotype among African Americans and European Americans. Prostaglandins Leukot Essent Fat Acids Rizzi F, Conti C, Dogliotti E, Terranegra A, Salvi E, Braga D, Ricca F, Lupoli S, Mingione A, Pivari F, Brasacchio C, Barcella M, Chittani M, D'Avila F, Turiel M, Lazzaroni M, Soldati L, Cusi D, Barlassina C Interaction between polyphenols intake and PON1 gene variants on markers of cardiovascular disease: a nutrigenetic observational study. J Transl Med 14 1 Rochette L, Zeller M, Cottin Y, Vergely C Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta 9 — Ros E Health benefits of nut consumption. Rostoff P, Szczeklik W, Piwowarska W, Konduracka E, Sanak M, Nessler J Association of common cyclooxygenase-2 COX-2 gene polymorphisms with clinical and angiographic characteristics of patients with coronary artery disease. Przegl Lek — Roy A, Rawal I, Jabbour S, Prabhakaran D Tobacco and cardiovascular disease: a summary of evidence. In: Cardiovascular, Respiratory, and Related Disorders. Rubio CP, Hernández-Ruiz J, Martinez-Subiela S, Tvarijonaviciute A, Ceron JJ Spectrophotometric assays for total antioxidant capacity TAC in dog serum: an update. Contractile function during angiotensin-II activation: increased NOX2 activity modulates cardiac calcium handling via phospholamban phosphorylation. NADPH oxidase-4 mediates protection against chronic load-induced stress in mouse hearts by enhancing angiogenesis. NADPH oxidases in heart failure: poachers or gamekeepers? Maack, C. Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment. Heymes, C. Increased myocardial NADPH oxidase activity in human heart failure. Dikalov, S. Angiotensin II-induced production of mitochondrial reactive oxygen species: potential mechanisms and relevance for cardiovascular disease. Varga, Z. Alternative splicing of NOX4 in the failing human heart. Duncan, J. Mitochondrial dysfunction in diabetic cardiomyopathy. Alsaied, T. Factors associated with long-term mortality after Fontan procedures: a systematic review. Heart , — Teshima, Y. Production of reactive oxygen species in the diabetic heart. Roles of mitochondria and NADPH oxidase. Schilling, J. The mitochondria in diabetic heart failure: from pathogenesis to therapeutic promise. Szabadkai, G. Physiology Bethesda 23 , 84—94 Dabkowski, E. Mitochondrial dysfunction in the type 2 diabetic heart is associated with alterations in spatially distinct mitochondrial proteomes. Flarsheim, C. Mitochondrial dysfunction accompanies diastolic dysfunction in diabetic rat heart. Trifunovic, A. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature , — Dai, D. Age-dependent cardiomyopathy in mitochondrial mutator mice is attenuated by overexpression of catalase targeted to mitochondria. Aging Cell 9 , — Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Shabalina, I. Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1. Aging Albany NY 9 , — Trinei, M. A pp66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene 21 , — Migliaccio, E. The p66shc adaptor protein controls oxidative stress response and life span in mammals. Rota, M. Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene. Res 99 , 42—52 Carpi, A. Akhmedov, A. Genetic deletion of the adaptor protein p66Shc increases susceptibility to short-term ischaemic myocardial injury via intracellular salvage pathways. Heart J. Boengler, K. Lack of contribution of p66shc and its mitochondrial translocation to ischemia—reperfusion injury and cardioprotection by ischemic preconditioning. Kaludercic, N. Monoamine oxidase A-mediated enhanced catabolism of norepinephrine contributes to adverse remodeling and pump failure in hearts with pressure overload. Res , — Monoamine oxidase B prompts mitochondrial and cardiac dysfunction in pressure overloaded hearts. Bianchi, P. Oxidative stress by monoamine oxidase mediates receptor-independent cardiomyocyte apoptosis by serotonin and postischemic myocardial injury. Borchi, E. Enhanced ROS production by NADPH oxidase is correlated to changes in antioxidant enzyme activity in human heart failure. Zhang, J. NOX4-dependent hydrogen peroxide overproduction in human atrial fibrillation and HL-1 atrial cells: relationship to hypertension. Sorescu, D. Superoxide production and expression of NOX family proteins in human atherosclerosis. Van Remmen, H. Knockout mice heterozygous for Sod2 show alterations in cardiac mitochondrial function and apoptosis. Shen, X. Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy. Diabetes 55 , — Lim, C. Glutathione peroxidase deficiency exacerbates ischemia-reperfusion injury in male but not female myocardium: insights into antioxidant compensatory mechanisms. Shiomi, T. Overexpression of glutathione peroxidase prevents left ventricular remodeling and failure after myocardial infarction in mice. Matsushima, S. Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular remodeling and failure after myocardial infarction in mice. Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and Galphaq overexpression-induced heart failure. Mitochondrial proteome remodelling in pressure overload-induced heart failure: the role of mitochondrial oxidative stress. Hornig, B. Vitamin C improves endothelial function of conduit arteries in patients with chronic heart failure. Circulation 97 , — Ellis, G. Acute effects of vitamin C on platelet responsiveness to nitric oxide donors and endothelial function in patients with chronic heart failure. Rimm, E. Vitamin E consumption and the risk of coronary heart disease in men. Stampfer, M. Vitamin E consumption and the risk of coronary disease in women. Cook, N. Lee, I. JAMA , 56—65 Virtamo, J. Effect of vitamin E and beta carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease. Tornwall, M. Effect of alpha-tocopherol and beta-carotene supplementation on coronary heart disease during the 6-year post-trial follow-up in the ATBC study. Nightingale, A. Chronic oral ascorbic acid therapy worsens skeletal muscle metabolism in patients with chronic heart failure. Heart Fail. Sochman, J. Infarct size limitation: acute N -acetylcysteine defense ISLAND trial : preliminary analysis and report after the first 30 patients. Horowitz, J. Combined use of nitroglycerin and N -acetylcysteine in the management of unstable angina pectoris. Circulation 77 , — Arstall, M. N -acetylcysteine in combination with nitroglycerin and streptokinase for the treatment of evolving acute myocardial infarction. Safety and biochemical effects. Circulation 92 , — Yesilbursa, D. Effect of N -acetylcysteine on oxidative stress and ventricular function in patients with myocardial infarction. Heart Vessels 21 , 33—37 Pasupathy, S. Early use of N-acetylcysteine with nitrate therapy in patients undergoing primary percutaneous coronary intervention for ST-segmentelevationmyocardial infarction reduces myocardial infarct size the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction]. Trnka, J. A mitochondria-targeted nitroxide is reduced to its hydroxylamine by ubiquinol in mitochondria. Free Radic. Dey, S. Mitochondrial ROS drive sudden cardiac death and chronic proteome remodeling in heart failure. Hoshino, A. Oxidative post-translational modifications develop LONP1 dysfunction in pressure overload heart failure. Ni, R. Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy. Kelso, G. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. Neuzil, J. Mitochondria transmit apoptosis signalling in cardiomyocyte-like cells and isolated hearts exposed to experimental ischemia—reperfusion injury. Redox Rep. Adlam, V. Targeting an antioxidant to mitochondria decreases cardiac ischemia - reperfusion injury. FASEB J. Ribeiro Junior, R. MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload. Szeto, H. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Chicco, A. Role of cardiolipin alterations in mitochondrial dysfunction and disease. Cell Physiol. Birk, A. The mitochondrial-targeted compound SS re-energizes ischemic mitochondria by interacting with cardiolipin. Hanske, J. Conformational properties of cardiolipin-bound cytochrome c. Zhao, K. Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert -butyl hydroperoxide in neuronal cell lines. Kloner, R. Heart Assoc. Cho, J. Potent mitochondria-targeted peptides reduce myocardial infarction in rats. Artery Dis. Brown, D. Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia. Global proteomics and pathway analysis of pressure-overload-induced heart failure and its attenuation by mitochondrial-targeted peptides. Sabbah, H. Chronic therapy with Elamipretide MTP , a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Gibson, C. EMBRACE STEMI study: a phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP on reperfusion injury in patients undergoing primary percutaneous coronary intervention. Download references. This work was supported by funding from the American Heart Association Scientist Development Grant 16SDG; J. Department of Pediatrics, Division of Cardiovascular Biology, Emory University School of Medicine, Atlanta, GA, , USA. Jessica N. Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, , USA. Emory College of Arts and Sciences, Emory University, Atlanta, GA, , USA. You can also search for this author in PubMed Google Scholar. Correspondence to Jennifer Q. Open Access This article is licensed under a Creative Commons Attribution 4. Reprints and permissions. Peoples, J. Mitochondrial dysfunction and oxidative stress in heart disease. Exp Mol Med 51 , 1—13 Download citation. Received : 29 November Accepted : 29 November Published : 19 December Issue Date : December Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Naunyn-Schmiedeberg's Archives of Pharmacology Skip to main content Thank you for visiting nature. Download PDF. Subjects Cardiomyopathies Cardiovascular diseases. Abstract Beyond their role as a cellular powerhouse, mitochondria are emerging as integral players in molecular signaling and cell fate determination through reactive oxygen species ROS. Introduction Reactive oxygen species ROS , including the superoxide anion, the hydroxyl radical, and hydrogen peroxide, are critical signaling molecules with important roles in both cardiac physiology and disease. Mitochondrial sources of ROS The mitochondrial respiratory chain is central to energy production as it couples electron transfer between respiratory chain complexes to proton transport across the mitochondrial inner membrane to generate the electrochemical gradient required for ATP synthesis. Full size image. Mitochondrial ROS scavenging systems To regulate oxidative stress created by mitochondrial ROS, mitochondria employ an intricate network of ROS scavenging systems that coordinately work to mitigate this stress Fig. Oxidative stress and heart disease IR injury Ischemic cardiac injury resulting from the sudden occlusion of a coronary vessel as occurs in myocardial infarction induces a cascade of tissue hypoxia and cellular ATP depletion. Heart failure While IRI-related ROS injury is acute and occurs in a matter of hours to days, ROS-related effects in HF are more chronic. Diabetic cardiomyopathy Cardiomyopathy in diabetic patients is associated with metabolic abnormalities related to high levels of circulating fatty acids as well as elevated fatty acid stores within cardiomyocytes. A specific role for mitochondrial ROS in cardiac disease pathogenesis: lessons from animal modeling The central role of mitochondrial ROS and heart disease is highlighted by a number of genetic models in which the modulation of either mitochondrial ROS production pathways or mitochondrial ROS scavenging systems has a significant impact on cardiac physiology and the development of cardiac disease summarized in Table 1. Table 1 Summary of animal models of mitochondrial ROS and cardiac disease pathogenesis. Full size table. ROS as a therapeutic target for heart disease In light of the strong links between elevated ROS, oxidative stress, and cardiac disease, ROS has emerged as an attractive target for therapy, with the goal of many drug-based strategies being to boost cellular antioxidant capacity and enhance ROS detoxification summarized in Table 2. Table 2 Summary of selected antioxidant therapies for cardiovascular diseases. Mitochondria-targeted antioxidant therapies In light of the limited success of general antioxidants in mitigating heart disease and the strong preclinical animal studies supporting the idea that limiting ROS production or enhancing ROS scavenging in the mitochondrial compartment can be highly beneficial to the heart, in recent years, considerable effort has been directed towards developing mitochondria-targeted antioxidants as pharmacological agents to ameliorate disease. Moving from the bench towards the bedside: mitochondria-targeted antioxidants in the clinical setting In light of the promising results of drug-based mitochondrial ROS scavenging in animal models of heart disease, there has been intense interest in translating these benefits into patients. Discussion In recent decades, significant progress has been made in developing therapeutics to preserve mitochondrial integrity and attenuate oxidative stress in heart disease. References Burgoyne, J. CAS PubMed Google Scholar Richardson, A. CAS Google Scholar Maulik, S. CAS PubMed Google Scholar Tsutsui, H. CAS PubMed Google Scholar Misra, M. CAS PubMed Google Scholar Liu, Q. PubMed PubMed Central Google Scholar Li, Y. CAS PubMed Google Scholar Ardanaz, N. CAS PubMed Google Scholar Chen, Z. CAS PubMed Google Scholar Hu, C. CAS PubMed Google Scholar Huang, Q. CAS PubMed PubMed Central Google Scholar Ye, Y.

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