ERK1/2 pathway-mediated norepinephrine regulates function of endothelial progenitor cells

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 concentrations were 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(P0.05).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) activated ERK1/2 pathway in a dose-dependent manner,which could also be blocked by 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.