Effects of transplantation of hypoxia-inducible factor-1α genemodified cardiac stem cells on cardiac function of heart failure rats after myocardial infarction.

Abstract

Objective:To evaluate the effects of transplantation of hypoxia-inducible factor-1α (HIF-1α) gene-modified cardiac stem cells (CSCs) on the cardiac function of heart failure rats after myocardial infarction (MI).Methods:Twenty-four Sprague–Dawley rats were randomly divided into three groups: HIF-1α-modified CSCs group, single CSCs group, and model group. The model of heart failure after MI was established by thoracotomy-left anterior descending coronary artery ligation, followed by injection of modified CSCs, single CSCs, and PBS, respectively, 2 weeks later. The results were observed 4 weeks later.Results:CSCs were infected with recombinant adenovirus. HIF-1α mRNA level of HIF-1α-enhanced green fluorescent protein (EGFP)+CSCs group significantly surpassed those of EGFP+CSCs and CSCs groups (p<0.001). Left ventricular ejection fractions (LVEFs) of HIF-1α+CSCs+MI and CSCs+MI groups significantly increased compared with the model group (p<0.001). The difference between LVEFs before and after transplantation was positively correlated with the survival rate of CSCs in infarction border zone (r=0.867, p<0.001). The apoptosis rate of HIF-1α+CSCs+MI group was significantly lower than that of CSCs+MI group (p=0.008). The expression of vascular endothelial growth factor protein in HIF-1α+CSCs+MI group significantly increased, compared with that of MI group (p<0.001). The capillary density of HIF-1α+CSCs+MI group significantly exceeded that of CSCs+MI group (p<0.001).Conclusion:Transplantation of either HIF-1α-modified CSCs or single CSCs reduced cardiomyocyte apoptosis in rats with heart failure after MI, promoted vascular regeneration in infarct area, and improved cardiac function. Particularly, HIF-1α-modified CSCs had more significant effects.