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Effect of atorvastatin on cardiac function and HGF/c-Met signaling pathway after acute myocardial infarction in diabetic rats
Authors:YAN Guang-dong  LI Zi-cheng  LI Jian-hao  ZHANG Zai-yong  ZHAO Shan-jun  ZHANG Wen-zhu
Institution:1.Department of Cardiology, Central Hospital of Panyu District, Guangzhou 511400, China;2.Department of Cardiology, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
Abstract:AIM: To investigate the effect of atorvastatin on myocardial apoptosis, ventricular remodeling and cardiac function after acute myocardial infarction (AMI) in diabetic rats, and to explore whether the effect is mediated by hepatocyte growth factor (HGF)/c-Met signaling pathway. METHODS: Diabetes in 70 male SD rats was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg). After 8 weeks, AMI was induced by the ligation of the left anterior descending coronary artery in the diabetic rats, and 32 surviving rats were divided into AMI group (n=16) and AMI+atorvastatin group (n=16, 20 mg·kg-1·d-1) at random. The similar surgical procedure was completed in sham group (n=11) without coronary ligation. Atorvastatin was given daily by gavage from the first day after AMI. Two weeks later, the cardiac function, pathological changes of myocardial tissues, myocardial apoptosis, and the expression of HGF and c-Met were compared among groups. RESULTS: AMI significantly reduced cardiac function, increased collagen volume fraction (CVF) and myocardial apoptotic index, and up-regulated the expression of HGF and c-Met at mRNA and protein levels in AMI control group (P<0.05). The cardiac function was improved, and CVF and myocardial apoptotic index were reduced by the treatment with atorvastatin, which also up-regulated the expression of HGF and c-Met (P<0.05). CONCLUSION: Atorvastatin significantly attenuates myocardial apoptosis and cardiac remodeling, and improves cardiac function after AMI in diabetic rats by further enhancing the activation of HGF/c-Met pathway.
Keywords:Diabetes mellitus  Acute myocardial infarction  Cardiac function  Hepatocyte growth factor  Atorvastatin  
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