Wang Chao-Yung, Liu Ping-Yen, Liao James K
Vascular Medicine Research Unit, Brigham and Women's Hospital and Harvard Medical School, Cambridge, MA 02139, USA.
Trends Mol Med. 2008 Jan;14(1):37-44. doi: 10.1016/j.molmed.2007.11.004.
Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is required for cholesterol biosynthesis, and are beneficial in the primary and secondary prevention of cardiovascular disease. Most of the benefits of statin therapy are owing to the lowering of serum cholesterol levels. However, by inhibiting HMG-CoA reductase, statins can also inhibit the synthesis of isoprenoids, which are important lipid attachments for intracellular signaling molecules, such as Rho, Rac and Cdc42. Therefore, it is possible that statins might exert cholesterol-independent or 'pleiotropic' effects through direct inhibition of these small GTP-binding proteins. Recent studies have shown that statins might have important roles in diseases that are not mediated by cholesterol. Here, we review data from recent clinical trials that support the concept of statin pleiotropy and provide a rationale for their clinical importance.
他汀类药物可抑制3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶，该酶是胆固醇生物合成所必需的，并且对心血管疾病的一级和二级预防有益。他汀类药物治疗的大部分益处归因于血清胆固醇水平的降低。然而，通过抑制HMG-CoA还原酶，他汀类药物也可抑制类异戊二烯的合成，而类异戊二烯是细胞内信号分子（如Rho、Rac和Cdc42）重要的脂质附着基团。因此，他汀类药物有可能通过直接抑制这些小GTP结合蛋白而发挥非胆固醇依赖性或“多效性”作用。最近的研究表明，他汀类药物可能在非胆固醇介导的疾病中发挥重要作用。在此，我们回顾了近期临床试验的数据，这些数据支持他汀类药物多效性的概念，并为其临床重要性提供了理论依据。
