Simvastatin‐sodium delays cell death of anoxic cardiomyocytes by inhibition of the Na+/Ca2+ exchanger

FEBS Letters

Atsma, Douwe E.¹  Bastiaanse, E.M.Lars¹  Kuijpers, Marinette M.C.¹  Van Der Laarse, Arnoud¹ 

[1] Department of Cardiology, University Hospital Leiden, PO Box 9600, 2300 RC Leiden, The Netherlands

关键词: Simvastatin-sodium;    Na+/Ca2+-exchanger;    Intracellular [Ca2+];    Anoxia;    Cell death;   

DOI  :  10.1016/0014-5793(94)80308-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

When incubated under anoxic conditions, cultured neonatal cardiomyocytes undergo cell necrosis. Simvastatin-sodium, the bioactive metabolite of simvastatin (a potent serum cholesterol-lowering drug), delayed the anoxia-induced myocyte necrosis in a dose-dependent manner. This beneficial effect of simvastatin-sodium could not be attributed to its cholesterol-lowering properties. We found that simvastatin-sodium, at concentrations of 20 and 50 μM, attenuated the rise in intracellular Ca²⁺ concentration ([Ca²⁺]_i) measured with Fura-2 in anoxic cardiomyocytes. In a test of sarcolemmal Na⁺/Ca²⁺ exchange activity, simvastatin-sodium attenuated the rise of[Ca²⁺]_i upon incubation in sodium-free buffer, which normally causes a reversal of Na⁺/Ca²⁺ exchange and cellular calcium overload. The inhibitory action of simvastatin-sodium on the sarcolemmal Na⁺/Ca²⁺ exchanger could well explain the cardioprotective effect of the drug on myocytes subjected to anoxia.

【 授权许可】

Unknown