Ito Matthew K, Talbert Robert L, Tsimikas Sotirios
University of California, San Diego School of Medicine, La Jolla, California, USA.
Pharmacotherapy. 2006 Jul;26(7 Pt 2):85S-97S; discussion 98S-101S; quiz 106S-108S. doi: 10.1592/phco.26.7part2.85S.
Because elevated serum cholesterol levels are strongly associated with coronary heart disease, cholesterol reduction by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (or statins) has been assumed to be the predominant, if not the only, mechanism underlying the beneficial effects of these drugs in cardiovascular diseases. Subgroup analyses of large clinical trials, however, have suggested that the beneficial effects of statins may extend to mechanisms beyond cholesterol reduction. Indeed, recent experimental and clinical evidence indicates that some of the cholesterol-independent or "pleiotropic" effects of statins may be mediated through improving or restoring endothelial function, enhancing the stability of atherosclerotic plaques, and decreasing oxidative stress and vascular inflammation.
由于血清胆固醇水平升高与冠心病密切相关，因此人们认为3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（即他汀类药物）降低胆固醇的作用即便不是这些药物对心血管疾病产生有益作用的唯一机制，也是主要机制。然而，大型临床试验的亚组分析表明，他汀类药物的有益作用可能扩展至降低胆固醇以外的机制。事实上，最近的实验和临床证据表明，他汀类药物的一些非胆固醇依赖性或“多效性”作用可能是通过改善或恢复内皮功能、增强动脉粥样硬化斑块的稳定性以及降低氧化应激和血管炎症来介导的。
