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Journal of Lipid Research, Vol. 47, 2575-2580, November 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Patient-Oriented Research

Ezetimibe inhibits the incorporation of dietary oxidized cholesterol into lipoproteins

Ilona Staprans^1,*,, Xian-Mang Pan^*,, Joseph H. Rapp^*,, Arthur H. Moser^*, and Kenneth R. Feingold^*,

^* Department of Veterans Affairs Medical Center, University of California, San Francisco, CA
Department of Surgery, University of California, San Francisco, CA
Department of Medicine, University of California, San Francisco, CA

Published, JLR Papers in Press, August 7, 2006.

¹ To whom correspondence should be addressed. e-mail: ilona.staprans{at}ucsf.edu

ABSTRACT

Oxidized cholesterol is present in significant quantities in the typical Western diet. When ingested, oxidized cholesterol is absorbed by the small intestine and incorporated into both chylomicrons and LDL, resulting in LDL that is more susceptible to further oxidation. Feeding studies in animal models and epidemiological studies in humans have suggested that oxidized cholesterol in the diet increases the development of atherosclerosis. In this study, we determined the effect of ezetimibe, a drug that inhibits small intestinal absorption of cholesterol, on the levels of oxidized cholesterol in the serum after a test meal containing oxidized cholesterol. We demonstrate that ezetimibe, 10 mg per day for 1 month, markedly reduced the levels (50% decrease) of oxidized cholesterol in the serum after feeding a test meal containing either -epoxy cholesterol or 7-keto cholesterol, two of the predominant oxidized cholesterols found in the diet. Moreover, the decrease in oxidized cholesterol in the serum was attributable to a decrease in the incorporation of dietary oxidized cholesterol into both chylomicrons and LDL. Because there was no decrease in postprandial triglyceride levels, we conclude that this decrease in oxidized cholesterol levels in the serum is attributable to decreased absorption and not to enhanced clearance. Whether this decrease in oxidized cholesterol absorption prevents or delays the development of atherosclerosis remains to be determined.

Supplementary key words oxidized lipoproteins • diet • cholesterol absorption • -epoxy cholesterol • 7-keto cholesterol

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