Pleiotropic Effects of 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Inhibitors: Candidate Mechanisms for Anti-Lipid Deposition in Blood Vessels

Author(s): T. Kumai, N. Matsumoto, Y. Koitabashi, Y. Takeba, S. Oonuma, S. Sekine, M. Tadokoro, S. Kobayashi.

Journal Name: Current Medicinal Chemistry - Cardiovascular & Hematological Agents

Volume 3 , Issue 3 , 2005

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Abstract:

The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are considered first-line therapeutic agents for the prevention of coronary heart disease and atherosclerotic disorders related to hypercholesterolemia. Statins inhibit lipid deposition in the aortic endothelium. Although it has been accepted that the statins are potent inhibitors of cholesterol biosynthesis in the liver and that they lower circulating cholesterol levels, several cholesterol-independent (pleiotropic) effects have been reported. The cholesterol-independent effects of statins involve normalization of the nitric oxide (NO)-NO synthase system, anti-inflammatory effects through the inhibition of cytokine/chemokine production, inhibition of vascular smooth muscle cell proliferation and migration, and inhibition of platelet thrombus formation/reduction of the thrombotic response. Some pleiotropic effects of statins may depend on the inhibition of the biosynthesis of farnesyl- and geranylgeranyl-nonsterol compounds from mevalonate in the cells. The Rho/Rho kinase pathway and the phospatidylinositol-3 kinase/Akt pathway mediate the pleiotropic effects of statins. As variations occur in absorption, metabolism, and excretion mechanisms due to the characteristics of specific statins including their hydrophilicity and lipophilicity, there are differences in the transfer mechanisms of statins into tissues. However, the pleiotropic effects occur regardless of statin hydrophilicity and lipophilicity. This review summarizes the pleiotropic effects of statins on lipid deposition in blood vessels.

Keywords: statins, pleiotropic effect, hydrophilicity, lipophilicity, transporter

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Article Details

VOLUME: 3
ISSUE: 3
Year: 2005
Page: [195 - 201]
Pages: 7
DOI: 10.2174/1568016054368223
Price: $58

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