THE POTENTIAL ROLE OF ANTIOXIDANTS IN THE PREVENTION OF ATHEROSCLEROSIS

Hypercholesterolemia attributable to increased plasma concentrations of low density lipoproteins is a well recognized risk factor for the premature development of coronary atherosclerosis in both experimental animals and humans. Recent studies have indicated that modifications to low density lipoprotein result in enhanced uptake of the modified lipoproteins by macrophages and lead to accelerated rates of lipid deposition and the creation of foam cells. Oxidation of low density lipoprotein has been shown to be one of the modifications which leads to uptake of this lipoprotein by scavenger receptors present on macrophages and results in intracellular lipid accumulation. Treatment of hypercholesterolemic animals with antioxidant drugs, including probucol, has been shown to reduce the development of atherosclerosis and xanthoma regression has been observed in patients with severe hypercholesterolemia treated with this drug. Epidemiologic studies support the view that low plasma concentrations of antioxidant vitamins, including vitamin E are associated with higher rates of coronary atherosclerosis in humans and that supplementation with vitamin E is associated with a decreased incidence of coronary artery disease. Prospective clinical trials to assess the potential benefit of antioxidant supplementation in high risk patients are currently in progress and these trials, when completed, should provide definitive information concerning the potential benefits to be derived from supplementation with antioxidant vitamins as an adjunctive therapy to prevent the premature development of atherosclerosis.