Journal Article

Vascular inflammation and activation: new targets for lipid lowering

M. Aikawa and P. Libby

in European Heart Journal Supplements

Published on behalf of European Society of Cardiology

Volume 3, issue suppl_B, pages B3-B11
Published in print May 2001 | ISSN: 1520-765X
Published online May 2001 | e-ISSN: 1554-2815 | DOI: http://dx.doi.org/10.1016/S1520-765X(01)90051-3
Vascular inflammation and activation: new targets for lipid lowering

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Inflammatory cells, including macrophages, in atheroma overexpress matrix metalloproteinases (MMPs) and tissue factor which contribute to plaque rupture and thrombosis. Activated smooth muscle cells (SMCs) in the plaque's fibrous cap also express MMPs and tissue factor. Lipid lowering appears to reduce the incidence of acute coronary events in patients by stabilizing atherosclerotic plaques. To improve mechanistic understanding, we tested the hypothesis that experimental manipulation of cholesterol level improves features of atheroma related to their propensity to provoke acute thrombotic complications. In rabbits with established atheroma, dietary lipid lowering reduced accumulation of macrophages expressing MMPs and increased collagen, a key determinant of plaque stability. Lipid lowering also decreased expression of tissue factor and its inducer, CD40 ligand. SMCs in the fibrous cap of rabbit atheroma expressed less MMP and tissue factor after lipid lowering. We have recently found that treatment with an HMG-CoA reductase inhibitor, cerivastatin, retards macrophage accumulation in atheroma of Watanabe heritable hyperlipidaemic (WHHL) rabbits, probably in part by suppressing proliferation. Macrophage expression of MMPs and tissue factor also decreased with cerivastatin treatment in vivo and in vitro. These results support the view that lipid lowering reduces acute thrombotic complications of atherosclerosis in patients by attenuating vascular inflammation.

Keywords: Lipid lowering; atheroma; atherosclerosis

Journal Article.  2438 words. 

Subjects: Cardiovascular Medicine

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