Cardiac FrzA Gene Transfection Attenuates Left Ventricle Remodeling Of Ischemic Heart Failure In Aging Mice

Objective: To evaluate the feasibility of recombinant adeno-associated virusserotype9carrying FrzA Gene transfection to ischemic heart failure mice to interveneWnt signal pathway in order to prevent and cure heart failure, which may support a newmethod for gene therapy. Methods:150of male C57BL/6J mice were divided intosham(SH) group(n=15), heart failure(HF) group(n=45), HF+rAAV9-GFP group(n=45),HF+rAAV9-FrzA group(n=45). Ligation of left coronary artery to create HF model andmice were received tail-vein injection of either rAAV9-GFP or rAAV9-FrzA. After4weeks echocardiography was performed. Expression of FrzA, Dvl-1, GSK3β, p-GSK3βand β-catenin by RT-PCR or Western Blot.Masson’s trichrome-stained to detectmyocardial fibrosis; the expression of I type and III type collagen were measured byimmunohistochemistry.Results: Compared with sham group, the cardiac function wasdecreased in other3groups(P＜0.05), but the cardiac function was improved inHF+rAAV9-FrzA group compared with HF group and HF+rAAV9-GFP group.rAAV9-FrzA was successfully transfected and expressed in mouse heart. Compared withSH group, the expression of Dvl-1, p-GSK3β and β-catenin were increased in other3groups (P＜0.05); compared with HF/HF+rAAV9-GFP groups, rAAV9-FrzA couldsignificantly decrease the expression of Dvl-1, p-GSK3β and β-catenin(P＜0.05);compared with sham group, the content of CVF, collagen I and III were significantlyincreased in other3groups; compared with HF/HF+rAAV9-GFP groups, the content ofCVF, collagen I and III were relatively decreased in rAAV9-FrzA group(P＜0.05).Conclusion: rAAV9-FrzA could be effectively transfected and expressed in heart.rAAV9-FrzA could inhibit the Wnt signal pathway in ischemic heart failure mice to attenuate left ventricle remodeling and improve cardiac function, which may support anew idea for gene therpy of heart failure.