Role of Arterial Wall Antioxidant Defense in Beneficial Effects of Exercise on Atherosclerosis in Mice

Meilhac, Olivier; Ramachandran, Sumathi; Chiang, Kenneth T.; Santanam, Nalini; Parthasarathy, S.

doi:10.1161/hq1001.097106

Cited by 107 publications

(98 citation statements)

References 52 publications

(36 reference statements)

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“…In addition, we observed an exercise-induced increase in aortic iNOS protein expression that was also observed in another study (61). Overall, exercise-related induction of scavenger enzymes observed in the present study was consistent with previous observations (28)(29)(30)(31)(32)(33). The mild oxidative stress induced by graduated exercise could be responsible for its beneficial effects on atherosclerosis, perhaps by inducing vascular antioxidant defenses.…”

Section: Discussionsupporting

confidence: 92%

“…Moreover, both plasma and tissue oxidative stress were reduced and eNOS expression was increased in the aorta of these animals. The induction of eNOS by exercise has been reported (32,36,59,60). In addition, we observed an exercise-induced increase in aortic iNOS protein expression that was also observed in another study (61).…”

Section: Discussionsupporting

confidence: 88%

“…Here, metabolic intervention with antioxidants and L-arginine induced beneficial effects in graduated exercised mice by further inhibiting atherogenesis. In another study (32), vigorous exercise together with vitamin E alone did not protect mice from atherosclerosis, and vitamin E administration partially inhibited exercise-induced increase in catalase. Thus, to achieve truly beneficial effects, the focus of attention needs to be on the right degree of exercise (graduated and moderate) and the ideal mixture of supplements (vitamin E together with vitamin C and L-arginine).…”

Section: Discussionmentioning

confidence: 92%

“…Paradoxically, exercise-induced oxidative stress could be potentially beneficial for vascular dysfunction and atherogenesis through the induction of arterial antioxidant responses. This induction of scavenger enzymes would not only minimize oxidative damage but also reduce in situ the generation of oxidants in different species, including humans (28)(29)(30)(31)(32)(33). Exercise can also stimulate endothelial NO synthase (eNOS) and increase NO bioavailability, representing an important mechanism by which exercise conveys benefit in vasculoprotection (34,35).…”

mentioning

confidence: 99%

“…Nevertheless, strenuous exercise may initiate an immune and vascular proinflammatory milieu (36). There is induction of catalase and eNOS in the aorta by vigorous exercise in hypercholesterolemic mice, and vitamin E supplementation in the exercised group does not appear to affect atherosclerosis (32). In contrast, several studies showed clear beneficial effects of vitamin E on lesion progression in hypercholesterolemic mice (37)(38)(39)(40).…”

mentioning

confidence: 99%

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Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice

Napoli

Williams-Ignarro

Nigris

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

102

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CorrectionsPHARMACOLOGY. For the article ''Beneficial effects of antioxidants and L-arginine on oxidation-sensitive gene expression and endothelial NO synthase activity at sites of disturbed shear stress,'' by Filomena de Nigris, Lilach O. Lerman, Sharon Williams Ignarro, Giacomo Sica, Amir Lerman, Wulf Palinski, Louis J. Ignarro, and Claudio Napoli, which appeared in issue 3, February 4, 2003, of Proc. Natl. Acad. Sci. USA (100, 1420-1425 first published January 13, 2003; 10.1073͞pnas.0237367100), the authors should have noted that Louis J. Ignarro developed and markets Niteworks, a dietary supplement of L-arginine, L-citrulline, vitamin E, and vitamin C. Dr. Ignarro is also a member of the Scientific Advisory Board of Herbalife, the distributor of Niteworks. The pathogenic mechanisms by which physical exercise influences atherosclerotic lesion formation remain poorly understood. Because vigorous physical training increases oxidative stress, this study tested the hypothesis that graduated and moderate physical exercise together with metabolic intervention (L-arginine and antioxidants) may contribute to increased vascular protection. Exercise training in mice was induced by graduated swimming. In hypercholesterolemic male mice on an atherogenic high-cholesterol diet, graduated and moderate exercise lowered plasma cholesterol and decreased atherosclerotic lesions compared with sedentary control mice. Antioxidants (1.0% vitamin E added to the chow and 0.05% vitamin C added to the drinking water) and L-arginine (6% in drinking water) supplementation to exercising hypercholesterolemic mice further and synergistically reduced atherosclerosis compared with untreated exercised mice. Arterial oxidation-specific epitopes and systemic oxidative stress were reduced by metabolic intervention. Graduated chronic exercise elicited an increase in production of nitric oxide through increased endothelial nitric oxide synthase expression and ameliorated scavenger activities. Thus, metabolic intervention with L-arginine and antioxidants together with graduated and moderate exercise training reduce atherosclerotic lesion formation.catalase ͉ nitric oxide synthase ͉ vitamin E ͉ oxidative stress ͉ low-density lipoprotein P hysical exercise is a deterrent of cardiovascular disease and atherogenesis in animal models (1-5). Exercise can also positively influence classical risk factors that are associated with coronary heart disease such as diabetes, hypertension, obesity, dyslipidemias, and endothelial dysfunction (6-8). The higher respiration rate during severe physical exercise leads to the generation of more free radicals than the endogenous antioxidant systems can scavenge (9), whereas moderate intensity aerobic exercise enhances endothelium dependent vasodilation in humans (10), and attenuates exercise-induced peroxidation (11) and cardiovascular mortality (12) in the elderly. Moreover, there is an inverse association between intensity of physical activity and the risk of coronary heart disease events (13). A metaanalysis of 51 con...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice

Napoli

Williams-Ignarro

Nigris

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

102

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Physical inactivity and cardiovascular risk: baseline observations from men and premenopausal women

Garelnabi

Veledar

Abramson

et al. 2010

Clinical Laboratory Analysis

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Cardiac Response to Oxidative Stress Induced by Mitochondrial Dysfunction

Kim

Nilius

Kim

et al. 2016

Reviews of Physiology, Biochemistry and Pharmacology

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The heart works without resting, requiring enormous amounts of energy to continuously pump blood throughout the body. Because of its considerable energy requirements, the heart is vulnerable to oxidative stress caused by the generation of endogenous reactive oxygen species (ROS). Therefore, the heart has effective regulatory and adaptive mechanisms to protect against oxidative stress. Inherited or acquired mitochondrial respiratory chain dysfunction disrupts energy metabolism and causes excessive ROS production and oxidative stress. The physiological cardiac response to oxidative stress can strengthen the heart, but pathological cardiac responses or altered regulatory mechanisms can cause heart disease. Therefore, mitochondria-targeted antioxidants have been tested and some are used clinically. In this review, we briefly discuss the role of mitochondrial DNA mutations, mitochondrial dysfunction, and ROS generation in the development of heart disease and recent developments in mitochondria-targeted antioxidants for the treatment of heart disease.

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Role of Arterial Wall Antioxidant Defense in Beneficial Effects of Exercise on Atherosclerosis in Mice

Cited by 107 publications

References 52 publications

Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice

Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice

Physical inactivity and cardiovascular risk: baseline observations from men and premenopausal women

Cardiac Response to Oxidative Stress Induced by Mitochondrial Dysfunction

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