© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability
Gachon Medical School, Heart Center, Division of Cardiology, 1198 Kuwol-dong, Namdong-gu, Inchon, 405-760 South Korea
* Corresponding author. Tel.: +82-32-460-3683; fax: +82-32-460-3117 kwangk{at}ghil.com
Clinical trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statin therapy demonstrate an improvement in cardiovascular end points and coronary stenosis. However, an improvement in cardiovascular end points and coronary stenosis is incompletely explained by the baseline or treated LDL cholesterol level. The beneficial effects of statins on clinical events may involve nonlipid mechanisms that modify endothelial function, smooth muscle cells, and monocyte-macrophage: vasomotor function, inflammatory responses, and plaque stability. Augmented bioactivity of NO by statin therapy either indirectly by its effect on lipoprotein levels and protection of LDL from oxidation, or directly by effects on NO synthesis and release, might account for enhancement of endothelium-dependent vasodilation. Recent experimental and animal studies have demonstrated that statins dose-dependently decrease smooth muscle cells migration and proliferation, independently of their ability to reduce plasma cholesterol. Moreover, statins are able to reduce the in vitro cholesterol accumulation in macrophages and expression of matrix metalloproteinase, resulting in plaque stability. These effects of statins were completely prevented by the addition of mevalonate and partially by all-trans farnesol and all-trans geranylgeraniol, confirming the specific role of isoprenoid metabolites, probably through prenylated proteins, in regulating these cellular events. Statins have been shown to prevent the activation of monocytes into macrophages, inhibit the production of pro-inflammatory cytokines, C-reactive protein, and cellular adhesion molecules. Statins decrease the adhesion of monocyte to endothelial cells. Accordingly, statins exert their cardiovascular benefits through a direct antiatherogenic properties in the arterial wall, beyond their effects on plasma lipids.
KEYWORDS Atherosclerosis; Endothelial function; Infection/inflammation; Statins
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