期刊
CIRCULATION RESEARCH
卷 93, 期 8, 页码 697-699出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.0000097262.21507.DF
关键词
mitochondria; statins; myocytes; nitric oxide; preconditioning
资金
- NHLBI NIH HHS [HLO 7227-27, R37 HL36957] Funding Source: Medline
3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can exert beneficial effects independently of serum cholesterol reduction by increasing the bioavailability of nitric oxide. However, it is unclear whether statins can exert such effects directly on cardiac myocytes and whether mitochondria are potential targets. Neonatal rat cardiac myocytes were cultured and subjected to oxidant stress (1 hour of 100 mumol/L H2O2). Mitochondrial membrane potential, a key determinant of cardiomyocyte viability, was assessed by flow cytometric analysis of tetramethylrhodamine ethyl ester (TMRE)-loaded cells. Hydrogen peroxide significantly reduced mitochondrial membrane potential. Incubation of the cardiac myocytes in simvastatin (greater than or equal to1 mumol/L) 1 hour before peroxide exposure significantly attenuated the loss of TMRE fluorescence. This effect was inhibited by the nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) or the ATP-sensitive mitochondrial potassium channel (mitoK(ATP)) blocker 5-hydroxydecanoate. Simvastatin attenuates mitochondrial membrane depolarization after exposure to oxidant stress. These findings provide primary evidence that myocytes can act as triggers and effectors in the cardioprotective cascade of simvastatin therapy. These results bear implications of statin therapy as a potential clinical application of pharmacological preconditioning.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据