ADACE2over Expression Ameliorate Ventricular Remodeling Of Post-myocardial Infarction In Rats

Aims:To investigate the effects of Adenovirus-ACE2（AdACE2） onventricular remodeling in rats underwent Acute myocardial infarction(AMI) and explore its possible protective mechanisms.Methods:Seventy-five Sprague-Dawley(SD) rats were randomly divided intoMI;MI+Normal-Saline(NS);MI+Adenovirus-EGFP(AdEGFP);MI+AdACE2and sham groups. AMI model was induced by left anterior descendingcoronary artery ligation through a lateral thoracotomy in rats. Rats in theMI+NS, MI+AdEGFP and MI+AdACE2groups received directintramyocardial injection of NS, AdEGFP and AdACE2, respectively. Ratsin the MI and SHAM groups received no injection. Four weeks later,cardiac tissue samples were obtained to measure the relative signalpathway proteins and ventricular remodeling parameters.Results:(1) Western blot analysis showed that the protein expression level ofACE2was significantly increasing in myocardial tissue, meanwhile ELISA analysis showed that the expression level of Ang (1-7) was increased;(2)Immunohistochemical and Western blot analysis showed that theexpression level of AngⅡ, Ang（1-7）and α-SMA were increased, but Ang（1-7） expression increased more significantly in MI+AdACE2group incomparison with the SHAM group.(3) Western blot analysis showed thatthe protein expression levels of MKP-1were increased in comparison withthe other groups; p-ERK, P38, α-SMA, TGF-β1protein expression and thehydroxyproline production were significantly decreased in MI+AdACE2group.Conclusion:ACE2overexpression could improve ventricular fibrosis andameliorate ventricular remodeling after MI probably by regulating RASand MAKPs activity.