Role of arterial wall antioxidant defense in beneficial effects of exercise on atherosclerosis in mice.
The mechanism(s) by which exercise reduces atherogenic risk remains unknown. This study tested the hypothesis that sustained exercise-induced oxidative stress may increase antioxidant defense in the arterial wall. Acute exercise induced an increase in antibodies to oxidatively modified proteins and catalase in the aortic walls of normal mice compared with sedentary control mice. In male atherogenic diet-fed low density lipoprotein (LDL) receptor-deficient mice, exercise lowered plasma cholesterol (15%) and decreased atherosclerotic lesions by 40% compared with values in sedentary control mice, with a concomitant increase in arterial catalase and endothelial NO synthase. Because these mice lack the LDL receptor, the results indicate that the LDL receptor might not be responsible for the exercise-induced lowering of plasma cholesterol. Vitamin E supplementation to exercising LDL receptor-deficient mice did not reduce atherosclerotic lesion formation significantly as opposed to lesion formation in untreated exercised mice. Moreover, vitamin E counteracted the beneficial effects of exercise by preventing the induction of aortic catalase activity and endothelial NO synthase expression. These results might indicate that although vitamin E might have prevented the exercise-induced oxidative stress, its availability in the artery was insufficient to prevent the atherosclerotic process. These results indicate that exercise-induced plasma oxidative stress could be responsible for the prevention of atherosclerosis by stimulating arterial antioxidant response. Furthermore, vitamin E supplementation could be deleterious in exercisers by inhibiting antioxidant enzyme buildup in the arterial wall.
Meilhac
O
O
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.
Ramachandran
S
S
Chiang
K
K
Santanam
N
N
Parthasarathy
S
S
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001158:Arteries / Q000187:drug effects / Q000201:enzymology*; D001161:Arteriosclerosis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis; D002374:Catalase / Q000096:biosynthesis; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D011973:Receptors, LDL / Q000235:genetics; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D001323:Autoantibodies; D011973:Receptors, LDL; D014810:Vitamin E; D002784:Cholesterol; D002374:Catalase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse