Improvement Of Heart Function In Postinfarction Heart Failure Swine Models After Hepatocyte Growth Factor Gene Transfer: Comparison Of Low-, Medium- And High-dose Groups

Improvement of heart function in postinfarction heart failure swine models after hepatocyte growth factor gene transfer:Comparison of low-,medium- and high-dose groupsObjective:To study the therapeutic effect and dose-effect relationship on postinfarction heart failure with different doses of adenovirus-mediated human hepatocyte growth factor(Ad₅-HGF) transference in swine models.Method:Totally 24 swine were randomly divided into 4 groups:(â…°) control group(null- Ads,1ml);(â…±)low-dose group(1×10⁹Pfu/ml Ad₅-HGF,1ml);(â…²)medium-dose group(5×10⁹Pfu/ml Ad₅-HGF,1ml); (â…³)high-dose group(1×10¹⁰Pfu/ml Ads-HGF,1ml).Four weeks after left anterior descending coronary artery(LAD)ligation,different doses of Ad₅-HGF were transferred in three therapeutic groups and null- Ad₅ was transferred in the control group via right coronary artery.Four and seven weeks after LAD ligation,Gate cardiac perfusion imaging was performed to evaluate cardiac perfusion and left ventricular ejection fraction(LVEF).Seven weeks after LAD ligation,the apoptotic index of cardiocyte was observed by TUNEL,the expression of Bcl-2,Bax,α-SMA and Factorâ…§in the border zones were evaluated by immunohistochemistry,respectively.Results:Four weeks after LAD ligation,no significant difference in the heart function was observed among four groups.Three weeks after Ad₅-HGF transfer,the improvement of cardiac perfusion and LVEF was obviously observed in three therapeutic groups,especially in the high-dose group.TUNEL assay showed that the medium- and high-dose groups had a obvious reduction in the apoptotic index compared with the control group,especially in the high-dose group.The expression of Bcl-2 protein was increased and the expression of Bax protein was inhibited in the medium- and high-dose groups compared with the control group, especially in the high-dose group.The vessel density for either Factorâ…§⁺ orα-SMA⁺ was increased in the high-dose group,followed by the medium-dose group when compared with the control group.There were no significant differene in inducing angiogenesis,reducing apoptosis and ameliorating heart function between the low-dose group and control group.Although no statistical difference was observed between the medium- and high-dose groups,the cardiac protective effects of the high-dose group were greater than the medium-dose group.Conclusion:Different doses of Ad₅-HGF injected via noninfarct-related artery could induce angiogenesis,reduce apoptosis and ameliorate heart function,and the cardiac protective effects of the high-dose group (1×10¹⁰Pfu Ad₅-HGF)were most significant.