Improved cardiac function after sarcoplasmic reticulum Ca2+-ATPase gene transfer in a heart failure model induced by chronic myocardial ischaemia

Abstract

Objective Chronic myocardial ischaemia (CMI) has become an important cause of heart failure (HF). The aim of this study was to examine the eff ects of sarco-endoplasmic reticulum calcium ATPase (SERCA2a) gene transfer in large HF animal models induced by CMI.Methods and results HF was induced in mini pigs by proximal left anterior descending coronary (LAD) ameroid constrictors. After confi rmation of myocardial perfusion defects and cardiac function impairment, animals were divided into 4 groups (each including 4 animals): the HF group; the HF+enhanced green fl uorescent protein (EGFP) group; the HF+SERCA2a group; and sham animals as a control group. rAAV1-EGFP and rAAV1-SERCA2a were injected intramyocardially to animals of the HF+EGFP and HF+SERCA2a groups separately. Sixty days after gene transfer, expressions of SERCA2a were examined, cardiac functions and changes of serum infl ammatory and neuro-hormonal factors were determined. The results demonstrated that 60 days after gene transfer, LVEF, Ev/Av and ± dp/dtmax of the HF+SERCA2a group increased signifi cantly (P < 0.05), along with an increase in SERCA2a protein expression (P < 0.05) compared with the HF/HF+EGFP groups. Serum concentrations of infl ammatory and neuro-hormonal factors were also decreased in the HF+SERCA2a group (P < 0.05).Conclusions Restoration of SERCA2a in myocardium of HF model induced by CMI could signi fi cantly improve cardiac function, suggesting its potential therapeutic signifi cance in CMI-related heart failure.