title: Glycation and oxidation: a role in the pathogenesis of atherosclerosis.
abstract: Reactions involving glycation and oxidation of proteins and lipids are believed to contribute to atherogenesis. Glycation, the nonenzymatic binding of glucose to protein molecules, can increase the atherogenic potential of certain plasma constituents, including low-density lipoprotein (LDL). Glycation of LDL is significantly increased in diabetic patients compared with normal subjects, even in the presence of good glycemic control. Metabolic abnormalities associated with glycation of LDL include diminished recognition of LDL by the classic LDL receptor; increased covalent binding of LDL in vessel walls; enhanced uptake of LDL by macrophages, thus stimulating foam cell formation; increased platelet aggregation; formation of LDL-immune complexes; and generation of oxygen free radicals, resulting in oxidative damage to both the lipid and protein components of LDL and to any nearby macromolecules. Oxidized lipoproteins are characterized by cytotoxicity, potent stimulation of foam cell formation by macrophages, and procoagulant effects. Combined glycation and oxidation, "glycoxidation," occurs when oxidative reactions affect the initial products of glycation, and results in irreversible structural alterations of proteins. Glycoxidation is of greatest significance in long-lived proteins such as collagen. In these proteins, glycoxidation products, believed to be atherogenic, accumulate with advancing age: in diabetes, their rate of accumulation is accelerated. Inhibition of glycation, oxidation, and glycoxidation may form the basis of future antiatherogenic strategies in both diabetic and nondiabetic individuals.
authors.affiliation: Medical University of South Carolina, Charleston 29425.
authors.forename: T J
authors.initials: TJ
authors.lastname: Lyons
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D008077:Lipoproteins, LDL; D003094:Collagen