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). HIF-1 α -modified Methods: Twenty-four Sprague–Dawley rats were randomly divided into three groups: 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,HIF-1 α 2 weeks later. The resultsHIF-1 α -enhancedwere observed 4 weeks later. Results: CSCs were infected with recombinant adenovirus. mRNA level of green fluorescent proteinHIF-1 α +CSCs+MI(EGFP)+CSCs group significantly surpassed those of EGFP+CSCs and CSCs groups (p<0.001). Left ventricular ejection fractions (LVEFs) of and CSCs+MI groups significantly increased compared with the model group (p<0.001). The difference between LVEFs before and after transplantation 1 α +CSCs+MIwas positively correlated with the survival rate of CSCs in infarction border zone (r=0.867, p<0.001). The apoptosis rate of HIF-HIF-1 α +CSCs+MIgroup was significantly lower than that of CSCs+MI group (p=0.008). The expression of vascular endothelialHIF-1 α +CSCs+MIgrowth factor protein in group significantly increased, compared with that of MI group (p<0.001). The capillary density of group significantly exceeded that of CSCs+MI group (p<0.001). Conclusion: Transplantation of either HIF-1α-modified CSCs or single CSCs reduced cardiomyocyteHIF-1 α -modifiedapoptosis in rats with heart failure after MI, promoted vascular regeneration in infarct area, and improved cardiac function. Particularly, CSCs had more significant effects.