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(Circulation. 2003;107:521.)
© 2003 American Heart Association, Inc.

Brief Rapid Communications

Vitamin E Reduces Progression of Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice With Established Vascular Lesions

Tillmann Cyrus, MD; Yuemang Yao, BSc; Joshua Rokach, PhD; Lina X. Tang, MD; Domenico Praticò, MD

From the Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia, Pa; and The Claude Pepper Institute and Department of Chemistry (J.R.), Florida Institute of Technology, Melbourne, Fla.

Correspondence to Domenico Praticò, MD, University of Pennsylvania, Biomedical Research Building 2/3, Room 812, 421, Curie Blvd, Philadelphia, PA 19104. E-mail domenico{at}spirit.gcrc.upenn.edu

Background— A growing body of evidence from animal studies supports the hypothesis that oxidative stress-mediated mechanisms play a central role in early atherogenesis. In contrast, clinical trials with antioxidant vitamins have not produced consistent results in humans with established atherosclerosis.

Methods and Results— Low-density lipoprotein receptor-deficient mice (LDLR KO) were fed a high-fat diet for 3 months to induce atheroma. At this time, 1 group of mice was euthanized for examination of atherosclerosis, and 2 other groups were randomized to receive high-fat diet either alone or supplemented with vitamin E for 3 additional months. At the end of the study, LDLR KO on a vitamin E-supplemented fat diet had decreased 8,12-iso-isoprostane (iP)F₂-VI and monocyte chemoattractant protein-1 levels, but increased nitric oxide levels compared with mice on placebo. No difference in lipid levels was observed between the 2 groups. Compared with baseline, placebo group had progression of atherosclerosis. In contrast, vitamin E-treated animals showed a significant reduction in progression of atherosclerosis.

Conclusions— These results demonstrate that in LDLR KO, vitamin E supplementation reduces progression of established atherosclerosis by suppressing oxidative and inflammatory reactions and increasing nitric oxide levels.

Key Words: atherosclerosis • antioxidants • lipids • inflammation • nitric oxide

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