Transfection of rAAV1-SERCA2a improves cardiac function of beagles with heart failure

AIM:To study the effects of recombinant adeno-associated virus type 1 (rAAV1)-sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) transfection on the cardiac function of beagles with heart failure (HF). METHODS:The beagles were used to make an animal model with heart failure after rapid right ventricular pacing (230 beats/min) for 30 d. A reduced rate (180 beats/min) was continuously applied for another 30 d. The beagles were divided into 4 groups (n=4): control group, HF group, HF+EGFP group and HF+SERCA2a group. rAAV1-EGFP and rAAV1-SERCA2a (both 1×1012 viral genomes) were intramyocardially injected into the animals in the latter 2 groups, respectively. RESULTS:After transfection for 30 d, the left ventricular systolic function in HF+SERCA2a group was similar to that in control group, and significantly higher than that in HF group (P<0.05). The ratio of SERCA2a mRNA/GAPDH mRNA was significantly higher in HF+SERCA2a group than that in HF group (P<0.05). The expression level of SERCA2a in the myocardial tissues was higher in HF+SERCA2a group than that in HF group (P<0.05). The apoptotic index of the cardiomyocytes and the protein expression of MMP-9 were much lower in HF+ SERCA2a group than those in HF group (P<0.05). No significant difference of all parameters was observed between HF group and HF+EGFP group. The mRNA level of phospholamban was unchanged. CONCLUSION:Transfection of SERCA2a improves the expression of SERCA2a, restores the cardiac function and inhibits left ventricular remodeling by reducing the cardiac cell apoptosis and the MMP-9 expression in the heart failure beagles.