Abstract
Rapid endothelialization is an effective way to treat intimal hyperplasia after intravascular stent implantation. Blood vessels and nerves coordinate with each other in function, while neurotrophin-3 (NT-3) is an important class of nerve growth factors. Our study found that NT-3 promoted endothelial progenitor cell (EPC) mobilization, and the proportion of EPCs in peripheral blood was increased by 1.774 times compared with the control group. Besides, NT-3 promoted the expression of stromal cell-derived factor-1α (SDF-1α), matrix metalloproteinase-9 (MMP9), and chemokine (C-X-C motif) receptor 4 (CXCR4) in EPCs, which increased by 59.89%, 74.46%, and 107.7%, respectively, compared with the control group. Transwell experiments showed that NT-3 enhanced the migration of EPCs by 1.31 times. Flow chamber experiments demonstrated that NT-3 captured more circulating EPCs. As shown by ELISA results, NT-3 can promote the paracrine of vascular endothelial growth factor, interleukin-8, MMP-9, and SDF-1 from EPCs. Such increased angiogenic growth factors further accelerated the closure of endothelial cell scratches. Additionally, EPC-conditioned medium in the NT-3 group significantly inhibited the proliferation of vascular smooth muscle cells. Then animal experiments also illustrated that NT-3 prominently accelerated the endothelialization of injured carotid artery. In short, NT-3 accelerated rapid reendothelialization of injured carotid artery through promoting EPC mobilization and homing.