The Study Of Cyclin-A2Transfected Via RAAV9for Myocardium Infarction Therapy

Objective:To determine whether or not exogenous Cyclin-A2via rAAV9promotes cardiac self-repair and restart cardiomyocytes cycle in vivo after MI. MethodsrEighty mice were randomly divided into three groups, Sham(n=20), MI+rAAV9-eGFP(n=30) and MI+rAAV9-Cyclin-A2(n=30).2×1011genome copies in200ul saline were delivered into the mice myocardium through the caudal vein one week before MI. The Sham group was injected with saline at same volume and time. Post MI observation was three weeks. Echocardiography was performed to evaluate heart function. Western Blot was used to detect the expression of Cyclin-A2,PCNA and H3P. Immunohistochemical and Immunofluorescence analysis were used to detect the expression and location of related proteins. Masson staining was used to check collagen volume to evaluate ventricular remodeling.Results:Western Blot showed that expression of Cyclin-A2started at two weeks and can at least last for four weeks after injection. Compared with Sham and adeno-null,there was a significant statistical difference with P value less than0.01. Expression of PCNA and H3P was higher in Cyclin-A2treated group than control group (P<0.05). C-Kit and Connexin43showed an increase in Cyclin-A2treated group, but no change in other two groups (P＜0.05). Immunohistochemistry showed that Cyclin-A2after transfection was located mainly in nucleus. A decreased level of collagen I and III was observed in Cyclin-A2treated group than Sham and adeno-null group (P=0.029) by Masson Triple Stain.Heart function in Cyclin-A2and Adeno-null group was decreased,However,improved function was observed in Cyclin-A2treated group. Conclusion:Delivery of Cyclin-A2via rAAV9through the caudal vein injection can effectively transfect mice myocardium and promote cardiac self-repair. Inhibition of ventricular remodeling and improvement of heart function were also observed.