BACKGROUND Chronic heart failure (CHF) is characterized by left ventricular dysfunction and altered autonomic control of cardiac function. This study aimed to investigate the effects of atorvastatin on left ventricular remodeling (LVR) and cardiac function in rats with isoproterenol-induced CHF and the possible mechanism. METHODS An isoproterenol-induced CHF model was established in rata, which were subsequently treated with atorvastatin. Echocardiography, hemodynamic, and left ventricular mass indexes were assessed. The mRNA expression of RhoA, Rho kinase, and endothelial nitric oxide synthase (eNOS) was determined by RT-qPCR. The protein expression of myosin-binding subunit (MBS), MBS-P, eNOS, phosphorylated-eNOS, RhoA, and Rho kinase was measured by Western blot analysis. The relative activity of NADPH oxidase, ROS, and NO was assessed by ELISA. RESULTS Isoproterenol-induced CHF rats treated with atorvastatin exhibited decreased left ventricular end-systolic dimension, left ventricular end-diastolic dimension, left ventricular end-diastolic pressure, left ventricular mass index, maximum fall rate of change in left ventricular pressure, heart rate (p < 0.001), expression of RhoA, Rho kinase, MBS and MBS-P (p < 0.01), and relative activity of NADPH oxidase, ROS and NO (p < 0.05) and increased left ventricular short axis fractional shortening, left ventricular end-systolic pressure, maximum rise rate of change in left ventricular pressure (p < 0.001) and expression of eNOS, and phosphorylated-eNOS ser1177 (all p < 0.05) compared with those of rats with isoproterenol-induced CHF. CONCLUSION We demonstrated that atorvastatin inhibits LVR and improves cardiac function in rats with isoproterenol-induced CHF through inhibition of the RhoA/Rho kinase signaling pathway.

中文翻译：

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阿托伐他汀通过调节RhoA / Rho激酶信号通路减轻异丙肾上腺素诱发的慢性心力衰竭大鼠的左心室重构。

背景技术慢性心力衰竭（CHF）的特征在于左心功能不全和心脏功能的自主控制改变。本研究旨在探讨阿托伐他汀对异丙肾上腺素诱发的CHF大鼠左心室重构（LVR）和心脏功能的影响及其可能的机制。方法在大鼠体内建立异丙肾上腺素诱发的CHF模型，随后用阿托伐他汀治疗。超声心动图，血流动力学和左心室质量指数进行了评估。通过RT-qPCR确定RhoA，Rho激酶和内皮型一氧化氮合酶（eNOS）的mRNA表达。通过蛋白质印迹分析测量了肌球蛋白结合亚基（MBS），MBS-P，eNOS，磷酸化-eNOS，Rho​​A和Rho激酶的蛋白表达。NADPH氧化酶，ROS，并且通过ELISA评估NO。结果阿托伐他汀治疗的异丙肾上腺素诱导的CHF大鼠的左心室收缩末期尺寸，左心室舒张末期尺寸，左心室舒张末期压力，左心室质量指数，左心室压力的最大下降率，心率（ p <0.001），RhoA，Rho激酶，MBS和MBS-P的表达（p <0.01）以及NADPH氧化酶，ROS和NO的相对活性（p <0.05）和左室短轴分数缩短，左室末端增加收缩压，左心室压力的最大上升速率（p <0.001）和eNOS的表达以及磷酸化的eNOS ser1177（均p <0.05）与异丙肾上腺素诱导的CHF大鼠相比。