Effect of cholesterol-rich diets with and without added vitamins E and C on the severity of atherosclerosis in rabbits.

Oxysterols as oxidation products of cholesterol are considered an atherogenic factor in the development of atherosclerosis in the arteries of cholesterol-fed rabbits. We compared the atherogenic effects of diets enriched either with 0.5% oxidized cholesterol (OC; characterized by high amounts of oxysterols) or with pure cholesterol (PC). The effects of antioxidant vitamins E and C added to the PC diet were also evaluated in view of their antioxidative properties for lipoproteins and cholesterol and how this could affect the severity of atherosclerosis. Four groups of rabbits were fed the following for 11 wk: 1) a nonpurified stock diet, 2) this stock diet plus 0.5% OC, 3) the stock diet plus 0.5% PC, and 4) the stock diet plus 0.5% PC and 1000 mg vitamin E and 500 mg vitamin C/kg diet (PC + antioxidants). The OC and PC diets were equally hyperlipidemic and hypercholesterolemic. The severity of atherosclerotic lesions was highest with the OC diet and lowest with the PC + antioxidants diet. The plasma oxysterol concentration was proportional to the severity of atherosclerosis in all three groups of cholesterol-fed rabbits. beta-Very-low-density-lipoprotein modification was minimized by vitamins E and C as indicated by its polyacrylamide gel electrophoretic pattern and its increased binding to the rabbit liver membrane in vitro. This study indicated that OC and PC were equally atherogenic but that the addition of antioxidants to the PC diet significantly reduced its severity, even when hypercholesterolemia persisted. This indicated that atherogenesis can result from an excessive accumulation of oxidation products of cholesterol in the plasma.