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Current Medicinal Chemistry

Eiditor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Endothelial Dysfunction, Oxidative Stress and Inflammation in Atherosclerosis: Beneficial Effects of Statins

Author(s): Vicente Lahera, Marian Goicoechea, Soledad Garcia de Vinuesa, Maria Miana, Natalia de las Heras, Victoria Cachofeiro and Jose Luno

Volume 14 , Issue 2 , 2007

Page: [243 - 248] Pages: 6

DOI: 10.2174/092986707779313381

Price: $58

Abstract

Atherosclerosis and its complications represent the major cause of death in developed countries. Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A [HMGCoA] reductase and consequently inhibitors of cholesterol biosynthesis. Statins have been described as the most potent class of drugs to reduce serum cholesterol levels. In clinical trials, statins are beneficial in primary and secondary prevention of coronary heart disease. Statins, were initially designed as cholesterol-lowering drugs. However, these drugs, besides their lipid-lowering properties, exert a number of protective effects on the cardiovascular system that emerged over the past years. The benefits observed with statin treatment appear to be greater than that might be expected from reduction in lipid levels alone, suggesting effects beyond cholesterol lowering. These cholesterol-independent effects have been called “pleiotropic”. The cholesterol-independent or “pleiotropic” effects of statins involve improvement of endothelial function, stability of atherosclerotic plaques, decrease of oxidative stress and inflammation, and inhibition of thrombogenic response. These pleiotropic effects of statins have been proposed as key properties of these drugs to reduce cardiovascular morbidity and mortality. The present review will emphasize the molecular mechanisms underlying the effects of statins on endothelial function and oxidative stress. In particular, inhibition of small GTP-binding proteins, Rho, Ras and Rac, which are regulated by isoprenoids [farnesyl pyrophosphate and geranylgeranyl pyrophosphate], seems to play an important role in mediating the pleiotropic effects of statins.

Keywords: HMGCoA reductase inhibitors, cholesterol, LDL, endothelial dysfunction, oxidative stress, inflammation, atherosclerosis, isoprenoids, GTP-proteins


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