Acta Pharm. 2014 Mar;64(1):105-15. doi: 10.2478/acph-2014-0004.
C57BL/6 mice with dilated cardiomyopathy (DCM) were randomly divided to receive placebo or pitavastatin at a dose of 1 or 3 mg kg-1d-1. After 8 weeks treatment, mice with dilated cardiomyopathy developed serious cardiac dysfunction characterized by significantly enhanced left ventricular end-diastolic diameter (LVIDd), decreased left ventricular ejection fraction (LVEF) as well as left ventricular short axis fractional shortening (LVFS), accompanied with enlarged cardiomyocytes, and increased plasma levels of N-terminal pro-B type natriuretic peptide (NT-proBNP) and plasma angiotensin II (AngII) concentration. Moreover, myocardium sarcoplasmic reticulum Ca2+ pump (SERCA-2) activity was decreased. The ratio of phosphorylated phospholamban (PLB) to total PLB decreased significantly with the down-regulation of SERCA- -2a and ryanodine receptor (RyR2) expression. Pitavastatin was found to ameliorate the cardiac dysfunction in mice with dilated cardiomyopathy by reversing the changes in the ratios of phosphorylated PLB to total PLB, SERCA-2a and RyR2 via reducing the plasma AngII concentration and the expressions of myocardium angiotensin II type 1 receptor (AT1R) and protein kinase C (PKC)b2. The possible underlying mechanism might be the regulation of myocardial AT1R-PKCb2-Ca2+ handling proteins.
C57BL/6 扩张型心肌病（DCM）小鼠被随机分为接受安慰剂或匹伐他汀治疗，剂量分别为 1 或 3mgkg-1d-1。经过 8 周的治疗，扩张型心肌病小鼠出现严重的心脏功能障碍，表现为左心室舒张末期直径（LVIDd）显著增大，左心室射血分数（LVEF）和左心室短轴缩短率（LVFS）降低，伴有心肌细胞增大，以及 N 端脑钠肽前体（NT-proBNP）和血浆血管紧张素 II（AngII）浓度升高。此外，心肌肌浆网 Ca2+泵（SERCA-2）活性降低。磷酸化磷蛋白（PLB）与总 PLB 的比值显著降低，同时 SERCA-2a 和兰尼碱受体（RyR2）表达下调。匹伐他汀通过降低血浆 AngII 浓度和心肌血管紧张素 II 型 1 受体（AT1R）和蛋白激酶 C（PKC）b2 的表达，改善扩张型心肌病小鼠的心脏功能障碍，从而逆转磷酸化 PLB 与总 PLB、SERCA-2a 和 RyR2 的比值变化。其潜在的作用机制可能是调节心肌 AT1R-PKCb2-Ca2+处理蛋白。
