on July 18, 2002
Arteriosclerosis, Thrombosis, and Vascular Biology. 2002
Published online before print July 18, 2002, doi: 10.1161/01.ATV.0000030360.72503.56
Published online before print July 18, 2002, doi: 10.1161/01.ATV.0000030360.72503.56
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Submitted on May 8, 2002
Accepted on June 28, 2002
Statins Reduce Inflammation in Atheroma of Nonhuman Primates Independent of Effects on Serum Cholesterol
Galina K. Sukhova *;
From the Leducq Center for Cardiovascular Research (G.K.S., P.L.), Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass, and Wake Forest University (J.K.W.), Winston-Salem, NC.
* To whom correspondence should be addressed. E-mail: gsukhova{at}rics.bwh.harvard.edu.
Objective—Some of the statin-induced reduction in cardiac events in patients with atherosclerosis may be derived from mechanisms independent of lipid lowering. This study tested in nonhuman primates whether statins can influence inflammation (indicated by vascular cell adhesion molecule-1, interleukin-1ß, tissue factor, and macrophages) and features of plaque stability (indicated by collagen and smooth muscle cells) independent of their effect on plasma cholesterol level.
Methods and Results—Adult male cynomolgus monkeys (n=12 per group) consumed an atherogenic diet for 12 months while receiving (1) no treatment (control), (2) pravastatin (Prava, 40 mg/kg per day), or (3) simvastatin (Simva, 20 mg/kg per day). Dietary cholesterol was adjusted to equalize plasma cholesterol levels among groups. Although the intima/media ratio in the abdominal aorta did not differ among groups, drug treatment reduced inflammation and features of plaque vulnerability. Macrophage content in the lesions of statin-treated animals was lowered (2.4-fold with Prava and 1.3-fold with Simva; both P<0.001 versus control). Furthermore, lesions had 
2-fold less vascular cell adhesion molecule-1, interleukin-1ß, and tissue factor expression in statin-treated versus control animals (P<0.005). Lesional smooth muscle cell and collagen content was 2.1-fold greater in the Prava-treated group (P<0.001) and 1.5-fold greater in the Simva-treated group (P<0.005) than in the control group.
Conclusions—In primates, these results provide further support for the beneficial effect of statins on plaque inflammation and stability in addition to cholesterol lowering.
Key words: atherosclerosis • statins • inflammation • macrophages • serum cholesterol
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