Transplantation of Endothelial Progenitor Cells in the Treatment of Coronary Artery Microembolism in Rats

As the impairment of myocardial microenvironments due to coronary microembolization (CME) compromises the treatment effect of percutaneous coronary intervention and leads to adverse prognosis, we hypothesized that endothelial progenitor cells (EPCs) transplantation could improve cardiac function in the condition of CME. Low- (2 × 10(5)) and high- (2 × 10(6)) dose rat bone marrow-derived EPCs were transplanted in a model of CME. To develop a CME model, rats were injected with autologous micro-blood-clots into the left ventricle. Echocardiograph was examined before and 1, 7, and 28 days after EPC transplantation; serum cardiac troponin I (cTNI), von Willebrand factor (vWF), and cardiac microRNA expression were examined one day after EPCs transplantation. Heart morphology and vascular endothelial growth factor (VEGF), vWF, and basic fibroblast growth factor (bFGF) expression were examined one day after EPC transplantation. After 10 days of culture inductions, BM-EPCs have high purity as confirmed by flow cytometry. Cardiac function reflected by left ventricular ejection fraction significantly decreased after CME treatment and rescued by low-dose EPC. Compared to the sham group, cTNI and vWF serum levels increased significantly after CME treatment and rescued by low-dose EPC and high-dose EPC. Low-dose EPC treatment decreased myocardial necrosis and fibrosis and elevated cardiac expression of VEGF and vWF, while decreasing the cardiac expression of bFGF. Low-dose EPC treatment significantly suppressed cardiac expression of microRNA-19a but significantly enhanced microRNA-21, microRNA-214, and microRNA-486-3p expression. In conclusion, our results indicate that low-dose EPC transplantation may play a proangiogenic, antifibroblast, antifibrosis, and antinecrosis role and enhance cardiac function in a rat model of CME through a microRNA-related pathway.