The role of reactive oxygen species in atherosclerosis.
Reactive oxygen species (ROS) are probably not only unintended, toxic side-products of oxygen metabolism in mammalian cells, they also have several important physiologic functions including antimicrobial killing, regulation of cellular proliferation and growth, and regulation of vascular tone. ROS are generated within the vessel wall by several mechanisms, including a vascular type of a NAD(P)H oxidase. ROS formation can be stimulated by mechanical stress, environmental factors, the peptide angiotensin II, cytokines, native low-density lipoproteins (LDL), and in the presence of catalytic metal ions. Their ability to modify LDL, react with endothelial-derived nitric oxide subsequently forming peroxynitrite, and amplify the expression of various genes important for leukocyte recruitment within the arterial wall are the basis of the oxidant injury theory of atherosclerosis. In animal studies, antioxidant therapy (probucol, butylated hydroxytoluene, N', N'-diphenylenediamide, vitamin E, superoxide dismutase) have been successfully used to prevent fatty streak formation, and to restore impaired nitric oxide-dependent vasorelaxation. In man, antioxidant therapy (e.g., supplementation with vitamin E) clearly increased the resistance of LDL to oxidative modification. Case-controlled and prospective clinical studies suggest a relation between baseline antioxidant plasma levels and/or antioxidant supplementation and risk of cardiovascular events. In one secondary prevention trial (randomized, blinded, placebo-controlled), vitamin E supplementation reduced significantly the risk for non-fatal myocardial infarctions. Before general recommendations can be made, results of further large-scale trials should be awaited.
Mügge
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Division of Cardiology, St. Josef-Hospital, Ruhr-University, Bochum, Germany. MueggeA@AOL.COM
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D017382:Reactive Oxygen Species / Q000502:physiology*
D017382:Reactive Oxygen Species