ERKl/2 pathway-mediated norepinephrine regulates function of endothelial progenitor cells / 第二军医大学学报

ABSTRACT

Objective: To analyze the effects of norepinephrine (NE) on the proliferation and migration of endothelial progenitor cells (EPCs) and the related mechanism. Methods: NE, adrenoceptor antagonist, and MAPK signal pathway blocker of various concentrationswere used to treat peripheral EPCs derived from healthy adults. The proliferation potential, migration capacity and activation of ERK1/2 were assessed after different treatments. Results: NE increased the proliferation potential of EPCs in a dose-dependent manner. The number of EPCs increased by (48.3±23.3)%, (70.5±35.6)%, (82.4±14.9)% and (100. 3±48. 1) % after treatment with NE at 0. 01 μmol/L, 0. 1 μmol/L, 1 μmol/L and 10 μmol/L, respectively. Addition of alpha adrenoceptor antagonist phentolamine, selective beta 2 adrenoceptor antagonist I127, JNK blocker SP600125 and ERK1/2 blocker A6355 could block the above effects of NE, and beta 1 adrenoceptor antagonist metoprolol and p38 blocker PD169318 failed to block the effects of NE. NE at 10 μmol/L significantly promoted the migration of EPCs (P<0. 05). These effects could be blocked by addition of phentolamine (10 μmol/L) and I127 (10 μmol/L), but not by addition of metoprolol. NE(0. 1, 1 and 10 μmol/L) activatedERK1/2 pathway in a dose-dependent manner, which could also be blockedby phentolamine and I127, but not by metoprolol. Conclusion: NE can increase the proliferation potential and migration capacity of EPCs via activating ERK1/2 pathway with alpha and beta 2 adrenoceptor.