Is lipid peroxidation relevant to atherogenesis?

Many lines of evidence suggest that LDL, the major carrier of blood cholesterol, becomes atherogenic as a result of oxidation (reviewed in refs. 1–3). One of the most persuasive observations is that structurally unrelated lipid-soluble antioxidants inhibit atherogenesis in animal models of hypercholesterolemia. For example, probucol, butylated hydroxytoluene, and N,N′-diphenyl-phenylenediamine all inhibit LDL oxidation in vitro, and retard the progression of atherosclerosis in hypercholesterolemic rabbits, mice, and quail. Moreover, probucol exerts a significant effect on thoracic atherosclerosis in primates with diet-induced hypercholesterolemia. These observations may be relevant to human disease, because a recent clinical trial of vitamin E suggests that antioxidant therapy inhibits the clinical sequelae of atherosclerosis (4).