Pleiotropic effects of statins.
Pleiotropic effects of statins.
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他汀类药物的多效性作用。
DOI：
10.4103/2230-8210.163106
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发表时间：
2015-09
影响因子：
--
通讯作者：
Vasnawala H
中科院分区：
文献类型：
--
作者：
Kavalipati N;Shah J;Ramakrishan A;Vasnawala H
他汀类或3-羟甲基戊二酰辅酶A(HMG CoA)还原酶抑制剂不仅阻止胆固醇的生物合成，而且还抑制必要的异戊二烯中间体的合成，如法尼基焦磷酸酯、香叶基焦磷酸酯、异戊基腺苷、多醇和泛醌、血红素A和核纤层蛋白的多异戊二烯侧链。这些异戊二烯类中间体是激活各种细胞内/信号蛋白所必需的--小三磷酸鸟苷结合蛋白RAS和类似RAS的蛋白，如Rho、Rab、Rac、Ral或Rap，它们在多种细胞过程中起着不可或缺的作用。由于他汀类药物抑制HMG辅酶A还原酶，导致循环中的异戊二烯中间体减少，从而阻止了这些信号蛋白的激活。因此，他汀类药物的多种作用，如抗炎作用、抗氧化作用、抗增殖和免疫调节作用、斑块稳定性、交感神经流出的正常化和防止血小板聚集，都是由于循环中的异戊二烯减少，从而使信号蛋白失活。他汀类药物的这些被称为他汀类多效性的多脂非依赖性作用可能会为多个治疗领域的研究打开闸门，引起全球研究人员和临床医生的注意。
Statins or 3-hydroxy-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors not only prevents the synthesis of cholesterol biosynthesis but also inhibits the synthesis of essential isoprenoid intermediates such as farnesyl pyrophosphate, geranylgeranyl pyrophosphate, isopentanyl adenosine, dolichols and polyisoprenoid side chains of ubiquinone, heme A, and nuclear lamins. These isoprenoid intermediates are required for activation of various intracellular/signaling proteins- small guanosine triphosphate bound protein Ras and Ras-like proteins like Rho, Rab, Rac, Ral, or Rap which plays an indispensible role in multiple cellular processes. Reduction of circulating isoprenoids intermediates as a result of HMG CoA reductase inhibition by statins prevents activation of these signalling proteins. Hence, the multiple effects of statins such as antiinflammatory effects, antioxidant effects, antiproliferative and immunomodulatory effects, plaque stability, normalization of sympathetic outflow, and prevention of platelet aggregation are due to reduction of circulating isoprenoids and hence inactivation of signalling proteins. These multiple lipid-independent effects of statins termed as statin pleiotropy would potentially open floodgates for research in multiple treatment domains catching attentions of researchers and clinician across the globe.