Endothelial dysfunction, oxidative stress and inflammation in atherosclerosis:: Beneficial effects of statins

被引:149
作者
Lahera, Vicente
Goicoechea, Marian
Garcia de Vinuesa, Soledad
Miana, Maria
de las Heras, Natalia
Cachofeiro, Victoria
Luno, Jose
机构
[1] Univ Madrid, Serv Nefrol, Hosp Gen Gregorio Maranon, Madrid 28007, Spain
[2] Univ Complutense, Dept Physiol, Sch Med, E-28040 Madrid, Spain
关键词
HMGCoA reductase inhibitors; cholesterol; LDL; endothelial dysfunction; oxidative stress; inflammation; atherosclerosis; isoprenoids; GTP-proteins;
D O I
10.2174/092986707779313381
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:243 / 248
页数:6
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