Autophagy is involved in the differentiation of epicardial progenitor cells into vascular smooth muscle cells in mice

Abstract

Most coronary smooth muscle cells(CoSMCs) are differentiated from epicardial progenitor cells(EPCs), but the specific mechanism is not fully investigated. Previous studies have shown that autophagy plays an important role for smooth muscle cells(SMCs) differentiation, yet whether autophagy is involved in the differentiation of EPCs into CoSMCs remains unclear. In the present study, We first isolated and cultured EPCs and continuously cultured them for 72 h. Then the autophagy induction and inhibition experiment was established by using the autophagy inducer Rapamycin(RAPA) and the inhibitor 3-Methyladenine(3-MA). And further animal experiments were conducted to observe the effects of autophagy on the development of coronary arteries. Our data showed that autophagy occurred in the differentiation of EPCs into SMCs. Over activation of autophagy may lead to early transient differentiation of EPCs, enhanced migration ability and weakened systolic function, but overall, CoSMC development is still inhibited. However, inhibition of autophagy may delay the differentiation of EPCs, thus reducing the number of coronary arteries. Together, all these processes indicate that autophagy may regulate the differentiation of EPCs into CoSMCs by affecting the time point of differentiation, and appropriate autophagy intensity is required during the development of CoSMCs.