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

Abstract

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 × 105) and high- (2 × 106) 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.

Endothelial colony-forming cell-derived exosomal miR-21-5p regulates autophagic flux to promote vascular endothelial repair by inhibiting SIPL1A2 in atherosclerosis

“…ECFCs have been shown to promote the formation of new endothelium in animal models, in which vessel injury occurs after balloon injury, myocardial infarction, or coronary microembolization [ 35 – 37 ]. Exosomes have emerged as an important paracrine mechanism of cell-to-cell communication by facilitating the transfer of RNAs or proteins from one cell to a recipient cell [ 38 ], and their use is currently considered to represent a promising alternative to stem cell therapy [ 39 ].…”

Comparative Preliminary Analysis of Umbilical Cord Blood-, Healthy Adult Peripheral Blood- and Myocardial Infarct Peripheral Blood-Derived Endothelial Progenitor Cells

“…EPCs have been reported, which have role in vasculogenesis, angiogenesis, and re-endothelialization of injured vessels. Recently, study by Xue et al indicates that even low-dose of EPCs transplantation may play a pro-angiogenic, anti-fibroblast, anti-fibrosis, and antinecrosis role and enhance cardiac function in a rat model [13]. The EPCs angiogenic potential limited by the absence of their natural biologic foundation, namely, smooth muscle pericytes also known as smooth muscle cells (SMCs); EPC-SMCs cell sheet transplantation attenuated myocardial dysfunction [14].…”

Regulation of Endothelial Progenitor Cell Functions in Ischemic Heart Disease: New Therapeutic Targets for Cardiac Remodeling and Repair

“…In a myocardial ischemia–reperfusion model, EPCs and EPC-derived conditioned medium enhanced tissue regeneration and improved ischemia-related organ dysfunction by inhibiting oxidative stress (oxidative proteins and markers of oxidative stress), autophagy (LC3B-I and LC3B-II), apoptosis (cleaved caspase 3 and cleaved PARP) and fibrosis (Smad3 and TGF-ß)-associated marker expression ( 116 ). Studies have shown that miR-214 expression was upregulated in EPCs and may have regulated CM Ca2+ homeostasis and cell survival during myocardial ischemia injury through miR-214 ( 117 , 118 ). Hong et al found that crosstalk between ECs and CMs was critical for regulating CM function and that vascular networks generated by ECFCs enhanced the engraftment of human pluripotent stem cells.…”

“…Reduced basic fibroblast growth factor and increased angiogenesis in ischemic hearts after EPC EX treatment reduced the area of cardiac fibrosis. Therefore, it was inferred that the proangiogenic function of EPC-derived EXs may be partially attributable of the activated MEndT of CFs ( 117 ). However, how EPC-derived EXs regulate the MEndT has not been elucidated to date.…”