Cardiovascular disease and nutrient antioxidants: role of low-density lipoprotein oxidation.
Increasing evidence indicates that oxidative modification of low-density lipoprotein (LDL) is causally related to atherosclerosis. Oxidatively modified LDL (oxLDL), in contrast to native LDL, is taken up avidly by macrophages, leading to formation of lipid-laden foam cells. Foam cells are pathognomonic of the atherosclerotic fatty streak. Modified LDL may also promote atherosclerosis by many other mechanisms, such as recruitment and retention of monocyte-macrophages, T-lymphocytes, and smooth muscle cells in the arterial intima, and cytotoxicity toward endothelial cells and macrophage-derived foam cells. The "oxidation hypothesis of atherosclerosis" is supported by a number of in vivo findings, such as the presence of oxLDL in atherosclerotic lesions, and increased titers of autoantibodies against modified LDL in patients with atherosclerosis. As a corollary of the oxidation hypothesis of atherosclerosis, antioxidants that can inhibit LDL oxidation may act as antiatherogens. This conception is supported by animal studies showing that antioxidants such as probucol, butylated hydroxytoluene, and alpha-tocopherol can slow the progression of atherosclerosis. Epidemiological and clinical data indicate a protective role of dietary antioxidants against cardiovascular disease, including vitamin E, beta-carotene, and vitamin C. Likewise, basic research studies on LDL oxidation have demonstrated a protective role for antioxidants, present either in the aqueous environment of LDL or associated with the lipoprotein itself. More studies are needed to establish the effectiveness and determine the required doses of specific antioxidants to prevent and possibly treat cardiovascular disease.
Frei
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Boston University School of Medicine, Whitaker Cardiovascular Institute, Massachusetts 02118, USA.
D000975:Antioxidants / Q000592:standards*; D001161:Arteriosclerosis / Q000378:metabolism / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000517:prevention & control*; D004032:Diet; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010084:Oxidation-Reduction
D000975:Antioxidants; D008077:Lipoproteins, LDL