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Document Details : Title: Improved cardiac function after sarcoplasmic reticulum Ca2+-ATPase gene transfer in a heart failure model induced by chronic myocardial ischaemia Author(s): W. Xin , X. Li , X. Lu , K. Niu , J. Cai Journal: Acta Cardiologica Volume: 66 Issue: 1 Date: 2011 Pages: 57-64 DOI: 10.2143/AC.66.1.2064967 Abstract : Objective: Chronic myocardial ischaemia (CMI) has become an important cause of heart failure (HF). The aim of this study was to examine the effects 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 confirmation 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 fluorescent 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 inflammatory 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 significantly (P < 0.05), along with an increase in SERCA2a protein expression (P < 0.05) compared with the HF/HF+EGFP groups. Serum concentrations of inflammatory 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 significantly improve cardiac function, suggesting its potential therapeutic significance in CMI-related heart failure. |