© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Oxidized Cholesterol in the Diet Accelerates the Development of Atherosclerosis in LDL Receptor– and Apolipoprotein E–Deficient Mice
From the Department of Veterans Affairs Medical Center and the Departments of Surgery (I.S., X-M.P., J.H.R.) and Medicine (C.G., K.R.F.), University of California, San Francisco.
Correspondence to Ilona Staprans, PhD, Lipid Research Laboratory (151L), VA Medical Center, San Francisco, CA 94121. E-mail stapan{at}itsa.ucsf.edu
Abstract—The aim of the current study was to determine whether oxidized cholesterol in the diet accelerates atherosclerosis in low density lipoprotein receptor– (LDLR) and apolipoprotein E– (apo E) deficient mice. Mice were fed either a control diet or a diet containing oxidized cholesterol. For LDLR-deficient mice, the control diet consisted of regular mouse chow to which 1.0% cholesterol was added. The oxidized diet was identical to the control diet except that 5% of the added cholesterol was oxidized. In apo E–deficient mice, the control diet contained 0.15% cholesterol, whereas in the oxidized diet, 5% of the added cholesterol was oxidized. LDLR-deficient and apo E–deficient mice were fed the experimental diets for 7 and 4 months, respectively. In mice fed the oxidized-cholesterol diets, the levels of oxidized cholesterol in sera were increased. At the end of the experiment, aortas were removed and atherosclerosis was assessed. We found that in LDLR-deficient mice, feeding of an oxidized-cholesterol diet resulted in a 32% increase in fatty streak lesions (15.93±1.59% versus 21.00±1.38%, P<0.03). Similarly, in apo E–deficient mice, feeding of an oxidized-cholesterol diet increased fatty streak lesions by 38% (15.01±0.92% versus 20.70±0.86%, P<0.001). The results of the current study thus demonstrate that oxidized cholesterol in the diet accelerates fatty streak lesion formation in both LDLR- and apo E–deficient mice.
Key Words: oxidized cholesterol • atherosclerosis • oxidized-lipid diet • cardiovascular disease
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