Effect of angiotensin-converting enzyme 2 over-expression on ventricular remodeling in rat model of myocardial infarction / 第二军医大学学报

ABSTRACT

Objective To investigate the effect of angiotensin-converting enzyme 2 (ACE2) over-expression on ventricular remodeling in rat model of acute myocardial infarction (AMI) and the related mechanisms. Methods Totally 75 male SPrague- Dawley ratswere randomlydivided into five groups (n = 15): Sham group, AMI group, AMI + normal saline (AMI+NS) group, AMI+adenovirus-EGFP (AMI + AdEGFP) group, and AMI+ adenovirus-ACE2 (AMI+AdACE2) group. AMI models were established by ligating the left anterior descending coronary artery of rats. Rats in the AMI+NS, AMI+AdEGFP and AMI+AdACE2 groups received intramyocardial injection of NS, AdEGFP and AdACE2 in five different infarction border zones, respectively. Rats in the Sham and AMI groups received no injection intervention. Four weeks later, left ventricular end-diastolic pressure (LVEDP) and heart weight/body weight (HW/BW) were examined. Myocardial structure changes and collagendeposition were evaluated histopathologically. The expression of angiotensin (Ang) n (Angn), Ang-(1-7) and crsmooth muscle actin (crSMA) proteins was assessed by immunohistochemical staining. The relative protein expression of ACE2, Srchomology2domain-containingprotein tyrosine phosphatase 1 (SHP-1), ERK1/2, p-ERK1/2, p38, p-p38, crSMA and transforming growth factor (TGF-fii) was measured by Western blotting analysis. Results (1) Compared with the other four groups, the protein expression levels of ACE2 and Ang-(1-7) were significantly increased in myocardial tissues in AMI+AdACE2 group (P<0. 05). (2) Compared with the Sham group, LVEDP, the values of HW/BW, collagen deposition, and the expression levels of AngH, Ang-(1-7), SHP-1, p-ERK1/2/ERK1/2, p-p38/p38, crSMA and TGF-(3i were all signficantly upgraded in AMI, AMI+NS and AMI+AdEGFP groups (P<0. 05). (3) Compared with AMI, AMI+NS and AMI +AdEGFP groups, the expression levels of Ang-(1-7) and SHP-1 were significantly increased in AMI+AdACE2 group (P<0. 05); while p-ERK1/2/ERK1/2, p-p38/p38, mSMA and TGF-(3i protein expression levelswere significantly decreased in AMI + AdACE2 group (P<0. 05). Conclusion This study suggests that over-expression of ACE2 can improve ventricular fibrosis and ameliorate ventricular remodeling after myocardial infarction in rats, which may be due to that ACE2 increases SHP-1 protein expression, and the latter negatively regulates renin-angiotensin system (RAS) and mitogen-activated protein kinases (MAKPs) pathway.