LOVASTATIN DECREASES COENZYME-Q LEVELS IN HUMANS
LOVASTATIN DECREASES COENZYME-Q LEVELS IN HUMANS
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DOI：
10.1073/pnas.87.22.8931
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发表时间：
1990-11-01
影响因子：
11.1
通讯作者：
TAMAGAWA, H
中科院分区：
文献类型：
--
作者：
FOLKERS, K;LANGSJOEN, P;TAMAGAWA, H
洛伐他汀在临床上用于治疗高胆固醇血症患者并成功降低胆固醇水平。洛伐他汀的作用机制是抑制 3-羟基-3-甲基戊二酰辅酶 A 还原酶，该酶参与从乙酰辅酶 A 生物合成胆固醇。抑制这种酶还可以抑制辅酶 Q10 (CoQ10) 的内在生物合成，但目前还没有关于洛伐他汀是否像降低胆固醇一样降低 CoQ10 水平的明确数据。洛伐他汀的临床用途是降低患心脏病的风险，如果洛伐他汀降低辅酶Q10的水平，这种降低将构成新的心脏病风险，因为已经确定辅酶Q10对于心脏功能是不可或缺的。我们进行了三个相关方案来确定洛伐他汀是否确实抑制 CoQ10 的生物合成。在大鼠身上进行了一项方案，并在前一篇论文中进行了报道 [Willis, R. A.、Folkers, K.、Tucker, J. L.、Ye, C.-Q.、Xia, L. -J.。和玉川 H. (1990) Proc。国家。阿卡德。科学。美国 87，''8928-8930]。此处报告了其他两个协议。其中一项涉及医院的患者，另一项涉及一名志愿者，他允许对 CoQ10、胆固醇水平和心脏功能进行特殊监测。三个方案的所有数据都表明洛伐他汀确实降低了 CoQ10 的水平。 5名住院患者，年龄43-72岁，发现洛伐他汀导致心脏病增加，这对于在洛伐他汀之前或服用洛伐他汀之后患有IV级心肌病的患者来说是危及生命的。口服 CoQ10 可以增加血液中 CoQ10 的水平，并且通常伴随着心脏功能的改善。尽管洛伐他汀是一种成功的药物，但它也有副作用，特别是包括肝功能障碍，这可能是由洛伐他汀引起的 CoQ10 缺乏引起的。
Lovastatin is clinically used to treat patients with hypercholesterolemia and successfully lowers cholesterol levels. The mechanism of action of lovastatin is inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme involved in the biosynthesis of cholesterol from acetyl-CoA. Inhibition of this enzyme could also inhibit the intrinsic biosynthesis of coenzyme Q10 (CoQ10), but there have not been definitive data on whether lovastatin reduces levels of CoQ10 as it does cholesterol. The clinical use of lovastatin is to reduce a risk of cardiac disease, and if lovastatin were to reduce levels of CoQ10, this reduction would constitute a new risk of cardiac disease, since it is established that CoQ10 is indispensable for cardiac function. We have conducted three related protocols to determine whether lovastatin does indeed inhibit the biosynthesis of CoQ10. One protocol was done on rats, and is reported in the preceding paper [Willis, R. A., Folkers, K., Tucker, J. L., Ye, C.-Q., Xia, L. -J. and Tamagawa, H. (1990) Proc. Natl. Acad. Sci. USA 87, ''8928-8930]. The other two protocols are reported here. One involved patients in a hospital, and the other involved a volunteer who permitted extraordinary monitoring of CoQ10 and cholesterol levels and cardiac function. All data from the three protocols revealed that lovastatin does indeed lower levels of CoQ10. The five hospitalized patients, 43-72 years old, revealed increased cardiac disease from lovastatin, which was life-threatening for patients having class IV cardiomyopathy before lovastatin or after taking lovastatin. Oral administation of CoQ10 increased blood levels of CoQ10 and was generally accompanied by an improvement in cardiac function. Although a successful drug, lovastatin does have side effects, particularly including liver dysfunction, which presumably can be caused by the lovastatin-induced deficiency of CoQ10.