Inhibition of the mevalonate pathway: Benefits beyond cholesterol reduction?
Inhibition of the mevalonate pathway: Benefits beyond cholesterol reduction?
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DOI：
10.1016/s0140-6736(96)90217-2
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发表时间：
1996-01-13
期刊：
影响因子：
168.9
通讯作者：
Kasiske, BL
中科院分区：
文献类型：
--
作者：
Massy, ZA;Keane, WF;Kasiske, BL
3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（HMG-CoA RIs）降低血浆总胆固醇和低密度脂蛋白胆固醇。临床研究表明，HMG-CoA RIs可降低动脉病变的严重程度和心血管疾病事件的频率。2,3通常认为HMG-CoA RIs的有益作用是由于竞争性抑制胆固醇合成所致然而，胆固醇只是HMG-CoA还原酶的产物甲羟戊酸的众多产物之一。甲羟戊酸代谢产生一系列类异戊二烯化合物，包括法尼基、香叶基和醇类异戊二烯是细胞增殖和其他重要细胞功能所必需的我们假设类异戊二烯的减少可以解释HMG-CoA RIs的一些有益作用。
3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HMG-CoA RIs) reduce plasma total and low-density lipoprotein cholesterol.1Clinical studies with HMG-CoA RIs have shown a reduction in severity of arterial lesions and frequency of cardiovascular disease events.2,3It is usually assumed that the beneficial effects of HMG-CoA RIs result from competitive inhibition of cholesterol synthesis.4 However, cholesterol is only one among many products of mevalonate, the product of HMG-CoA reductase. Mevalonate metabolism yields a series of isoprenoid compounds, including farnesyl, geranylgeranyl, and dolichol.4 Isoprenoids are necessary for cell proliferation and other important cell funtions.4 We hypothesise that reduction of isoprenoids may explain some of the beneficial effects of HMG-CoA RIs.