Jasińska Magdalena, Owczarek Jacek, Orszulak-Michalak Daria
Department of Biopharmacy, Medical University of Łódź, Muszyńskiego 1, PL 90-151 Łódź, Poland.
Pharmacol Rep. 2007 Sep-Oct;59(5):483-99.
In the recent years, 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibitors have emerged as the most important class of lipid-lowering agents. Through inhibition of HMG-CoA reductase, they restrict the rate-limiting step of cholesterol synthesis resulting in up-regulation of low density lipoproteins (LDL) receptors on the cell membrane and reduction of atherogenic LDL consequences. The wide spectrum of non-lipid-mediated pleiotropic effects of statins includes: improvement of endothelial dysfunction, increased nitric oxide bioavailability, antioxidant effects, anti-inflammatory and immunomodulatory properties, stabilization of atherosclerotic plaques and inhibition of cardiac hypertrophy. Several clinical trials have demonstrated and confirmed these beneficial effects of statins in cardiovascular disorders, in primary and secondary prevention settings. Recent studies have reported that the physiological background of the widespread therapeutic efficacy of HMG-CoAreductase inhibitors involved various mechanisms, partially associated with statin impact on posttranslational modifications (e.g. prenylation process). In this review, we have focused on some of them, especially including the statin impact on the endothelial dysfunction and inflammation, peroxisome poliferator-activated receptor (PPAR), beta-adrenergic signaling, renin-angiotensin system and their possible mutual mechanistic linkage.
近年来，3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂已成为最重要的一类降脂药物。通过抑制HMG-CoA还原酶，它们限制了胆固醇合成的限速步骤，导致细胞膜上低密度脂蛋白（LDL）受体上调，并减少致动脉粥样硬化性LDL的产生。他汀类药物广泛的非脂质介导的多效性作用包括：改善内皮功能障碍、增加一氧化氮生物利用度、抗氧化作用、抗炎和免疫调节特性、稳定动脉粥样硬化斑块以及抑制心脏肥大。多项临床试验已证实并确认了他汀类药物在心血管疾病的一级和二级预防中的这些有益作用。最近的研究报告称，HMG-CoA还原酶抑制剂广泛治疗效果的生理背景涉及多种机制，部分与他汀类药物对翻译后修饰（如异戊二烯化过程）的影响有关。在本综述中，我们重点关注了其中一些机制，特别是他汀类药物对内皮功能障碍和炎症、过氧化物酶体增殖物激活受体（PPAR）、β-肾上腺素能信号传导、肾素-血管紧张素系统及其可能的相互机制联系的影响。
