Oxidized Cholesterol in the Diet Accelerates the Development of Aortic Atherosclerosis in Cholesterol-Fed Rabbits

From the Department of Veterans Affairs Medical Center; and the Departments of Surgery and Medicine, University of California, San Francisco.

Correspondence to Ilona Stapr¯ans, PhD, Lipid Research Laboratory (151L), VA Medical Center, San Francisco, CA 94121.

Abstract—Oxidized lipoproteins may play a role in atherosclerosis. Recently, we have demonstrated that the levels of oxidized fatty acids in the circulation correlate directly with the quantity of oxidized fatty acids in the diet and that dietary oxidized fatty acids accelerate atherosclerosis in rabbits. The present study tests the hypothesis that oxidized cholesterol in the diet accelerates the development of atherosclerosis. Rabbits were fed a diet containing 0.33% nonoxidized cholesterol (control diet) or the same diet containing 0.33% cholesterol of which 5% was oxidized (oxidized diet). Serum cholesterol levels increased to a similar extent in both groups, with the majority of cholesterol in the ß-VLDL fraction. Moreover, in the serum ß-VLDL fraction and liver, there was a significant increase in the oxidized cholesterol levels. Most importantly, feeding a diet enriched in oxidized cholesterol resulted in a 100% increase in fatty streak lesions in the aorta. Western diets contain high concentrations of oxidized cholesterol products, and our results suggest that these foods may be a risk factor for atherosclerosis.

Key Words: oxidized cholesterol • ß-VLDL • atherosclerosis • oxidized diet

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