Free radical mediated oxidation of low-density lipoproteins (LDL), which has been extensively studied in the last two decades, plays a central role in the development of the atherosclerotic plaque. Oxidation involves the lipid moiety of LDL in a chain reaction mechanism. In the initial phase, free radicals preferentially attack highly oxidizable polyunsaturated fatty acids. Subsequent recruitment of other molecules includes cholesterol and phospholipids. The process of oxidation is counteracted by antioxidants present in LDL. By-products formed during oxidation of LDL lipids, which may have biological activity, react with amino acid residues of the LDL protein backbone with the consequent modification of chemical and immunological properties responsible for cellular receptor shift. Oxidation-altered apolipoprotein B of oxidized LDL is, in fact, recognized by the macrophage scavenger receptor responsible for foam cell formation. The mechanism of LDL oxidation and the impact on atherogenesis are discussed.
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