Submitted on June 15, 2006
Revised on August 1, 2006
Accepted on August 6, 2006
Ezetimibe inhibits the incorporation of dietary oxidized cholesterol into lipoproteins
Ilona Staprans, Xian-Mang Pan, Joseph H. Rapp, Arthur H. Moser, and Kenneth R. Feingold
Surgery, VA Medical Center (112G), San Francisco, CA 94121
Corresponding Author: ilona.staprans{at}ucsf.edu
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 which 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 the present 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 following a test meal containing oxidized cholesterol. We demonstrate that ezetimibe, 10mg per day for one month, markedly reduced the levels (50% decrease) of oxidized cholesterol in the serum after feeding a test meal containing either ?-epoxycholesterol or 7-ketocholesterol, two of the predominant oxidized cholesterols found in the diet. Moreover, the decrease in oxidized cholesterol in the serum is due to a decrease in the incorporation of dietary oxidized cholesterol into both chylomicrons and LDL. Since there was no decrease in the postprandial triglyceride levels, we conclude that this decrease in oxidized cholesterol levels in the serum is due to decreased absorption and not enhanced clearance. Whether this decrease in oxidized cholesterol absorption prevents or delays the development of atherosclerosis remains to be determined.
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