Simvastatin promotes atherosclerotic plaque stability in apoE-deficient mice independently of lipid lowering.
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.


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.
Bea
Florian
F
Department of Pathobiology, Interdisciplinary Graduate Program in Nutritional Sciences, University of Washington, Seattle 98195, USA.
Blessing
Erwin
E
Bennett
Brian
B
Levitz
Michael
M
Wallace
Elizabeth P
EP
Rosenfeld
Michael E
ME
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000097:blood / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D018450:Disease Progression; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008055:Lipids / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012044:Regression Analysis; D019821:Simvastatin / Q000493:pharmacokinetics*; D013997:Time Factors
D001057:Apolipoproteins E; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D002784:Cholesterol; D019821:Simvastatin