Therapy Effects Of Adeno-associated Virual Gene Transfer Of SERCA2a On Chronic Heart Failure Rats

Objective: To study the therapy effects of adeno-associated virual gene transfer of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a) on chronic heart failure(CHF) in 10 and 30 days, and the possible mechanisms of the therapy effects. To understand the pathophysiological mechanisms of chronic heart failure further.Methods: The rats were divided two groups: 10 days and 30 days after gene transfer. And each group was divided four sub-groups: control group, HF group, Group HF+EGFP, Group HF+SERCA. Chronic heart failure rats were obtained by creating descending aortic constriction. 0.9% sodium chloride solution, recombinant adeno-associated virus carrying enhanced green fluorescent protein (eGFP) gene and recombinant adeno-associated virus carrying SERCA2a gene, were respectively injected into pericardium of heart failure rats in different groups by intrapericardial injection with a trans-diaphragmatic approach. Then at 10 and 30 days after gene transfer, hemodynamic parameters , the protein expression of SERCA2a and the SERCA2a activity were measured and analyzed respectively. The difference of proteome of hearts was detected by expression proteomics between rats in Group HF+SERCA and those in HF group at 30 days after gene transfer. Electrophoretic sepatation and quantitation of cardiac myosin heavy chain isoforms of hearts were done in rats in different sub-groups at 30 days after gene transfer.Results: Gene transfer of SERCA2a in CHF rats increased the protein expression and activity of SERCA2a gradually. At 10 days after gene transfer, the protein expression and activity of SERCA2a were increased by 71% and 92% respectively, but still lower than those in the control rats. And at 30 days after gene transfer, the protein expression and activity of SERCA2a reached to the level of the control rats. The heart function was also improved along with the increase of SERCA2a expression and activity. The systolic and diastolic functions were enhanced significantly at 10 days,...