Endothelial progenitor cell (EPC) transplantation improves myocardial infarction via up-regulation of vascular endothelial growth factor and gap junction protein connexin 43 in rats

Background: Myocardial infarction (MI) has become one of the most deadly diseases worldwide. Therapeutic angiogenesis promotes the growth of capillary and collateral circulation, and therefore is considered a promising therapeutic method for MI by recovering the myocardial blood flow in the infarcted area. This study aimed to investigate the angiogenic effect and potential mechanism of endothelial progenitor cell (EPC) transplantation on in a rat model of MI. Methods: SD rats were randomly divided into healthy control, sham-operated, model and EPC group (n = 10 each). Model group was subjected to ligation of the anterior descending coronary artery. EPC group was treated by injection of immunofluorescence-confirmed EPC in the infarct following the construction of MI model. Sham-operated and model group was injected with same volume of saline. At 4 weeks after operation, ECG test and histological examination was performed. Myocardial apoptosis was detected by TUNEL assay. The expression of vascular endothelial growth factor (VEGF) and gap junction protein connexin 43 (Cx43) protein and mRNA was determined by immunohistochemical and qRT-PCR analyses, respectively. Results: When compared with model group, the EPC group exhibited lower VP, VT, VF and aggregate score (P = 0.006) at 4 week postoperatively. The myofibroblasts and cellular structure in EPC group was markedly recovered, and the vascular density in the infarct was significantly increased (P = 0.005). The myocardial apoptosis rate was markedly decreased (P = 0.002). The Cx43 and VEGF protein and mRNA expression was significantly enhanced (all P < 0.01). Conclusion: We confirm the therapeutic effects of EPC transplantation on MI, which might be achieved through stimulation of angiogenesis. Our study provides a theoretic basis for the clinical application of EPC transplantation in the treatment of MI.