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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1832.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Simvastatin Promotes Atherosclerotic Plaque Stability in ApoE-Deficient Mice Independently of Lipid Lowering

Florian Bea; Erwin Blessing; Brian Bennett; Michael Levitz; Elizabeth P. Wallace; Michael E. Rosenfeld

From the Departments of Pathobiology, Interdisciplinary Graduate Program in Nutritional Sciences (F.B., E.B, B.B., E.P.W., M.E.R.) and Biostatistics (M.L.), University of Washington, Seattle.

Correspondence to Michael E. Rosenfeld, PhD, Department of Pathobiology and Interdisciplinary Graduate Program in Nutritional Science, Box 353410, University of Washington, Seattle, WA 98195. E-mail ssmjm{at}u.washington.edu

Objective— This study sought to determine whether simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has stabilizing effects on vulnerable atherosclerotic plaques that are independent of their lipid-lowering capabilities.

Methods and Results— Simvastatin (50 mg/kg per day) was administered to 30-week-old apolipoprotein E–deficient mice exhibiting advanced unstable atherosclerotic lesions within the innominate/brachiocephalic artery. Simvastatin was administered in the chow to separate groups of mice for 6, 12, 18, or 24 weeks. Simvastatin significantly increased serum cholesterol after 12, 18, and 24 weeks of treatment. The average cross-sectional area of atherosclerotic lesion increased in the innominate artery after 12 and 24 weeks of treatment, concomitant with the increase in serum cholesterol. However, histological analysis of sections of the innominate artery stained with Movat and von Kossa stains demonstrated a 49% reduction in the frequency of intraplaque hemorrhage and a 56% reduction in the frequency of calcification, both markers of advanced and unstable atherosclerotic plaques.

Conclusions— These data suggest that despite an increase in serum cholesterol and lesion size, simvastatin has stabilizing effects on advanced atherosclerotic lesions.

Key Words: arteriosclerosis • statins • lipids • plaque stability

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