Therapeutic effects of adeno-associated virus gene mediated transfer of SERCA2a on beagle dogs with heart failure / 解放军医学杂志

ABSTRACT

Objective To investigate the therapeutic effects of recombinant adeno-associated virual gene serotype 1(rAAV1) mediated transfer of sarcoplasmic reticulum Ca2+ ATPase(SERCA2a) on beagle dogs with heart failure(HF).Methods The chronic HF model was reproduced in beagle dogs by giving rapid right ventricular pacing(230 beats/min) for 30 days.A reduced rate(180 beats/min)was continued for another 30 days.Sixteen beagle dogs were divided into four groups(4 each) control group,HF group,HF+EGFP group and HF+SERCA2a group.After rapid pacing for 30 days,rAAV1-EGFP(1?1012vg/ml) and rAAV1-SERCA2a(1?1012vg/ml) were respectively delivered via intramyocardial routes,while no treatment was given to the animals in both control and HF groups.At the end of the study,haemodynamics,echocardiography and the protein expression of SRCA2a were measured respectively.The apoptosis index of cardiac myocyte was evaluated by TUNEL.Bax expression was assessed by immunohistochemistry.Results After gene transfer of SERCA2a in HF beagle dogs for 30 days,the heart function was improved along with an increase in SERCA2a expression.Left ventricular systolic function was significantly increased,including the left ventricular systolic pressure(LVSP),left ventricular maximal rate of pressure rise(LV+dp/dtmax),left ventricular maximal rate of pressure decline(LV-dp/dtmax,P