Role Of MEK/ERK And PI3K/AKT Signaling Pathway On Expression Of VEGF In Human Umbilical Vein Endothelial Cells After Low-energy Extracorporeal Shock Wave

Background:In recent years,extracorporalcardiac shock wave therapy(ECSW) has been considered as an effective,safe and noninvasive angiogenetic strategy in Cardiovascular medicine. Experimental studies have reported that a low level of 0.09 mJ/mm2 SW enhanced the expression of vascular endothelial growth factor (VEGF) in vitro and in vivo; It also can significantly enhance ischemic myocardium angiogenesis and promte the collateral circulation regeneration.However,the mechanism remains unclear.Objective:we investigate whether MEK/ERK and PI3K/AKT signaling pathway play an important role in ECSW inducing VEGF.Methods:The HUVECs cell lines in vitro were divide into seven groups:the control group was neither treated with 0.09mJ/mm2 shock wave nor inhibitors (PD98059,Ly294002);solvent control group was just added DMSO.PD98059 group and Ly294002 group were performed with PD98059(30uM) and Ly294002 (30uM),respectly.Other groups were performed 0.09 mJ/mm2 shock wave with or without inhibitors(PD98059 or Ly294002). Western blotting was utilized to detect the changes in protein of VEGF、pERK1/2、ERK1/2、pAkt、Akt after incubation for 24 hours.Results:The p-AKT protein level of ECSW treatment group was obviously higher than the control group (P=0.001),while the p-ERK protein level of ECSW treatment group showed no significant change compared with the the non-treated control(P> P=0.224). The expression of VEGF in ECSW treatment group was obviously higher than the control group (P=0.003).Moreover,The expression of VEGF in PD98059+ECSW treatment group was obviously reduced than the ECSW group (P=0.002). The expression of VEGF in Ly294002+ECSW treatment group showed no significant change compared with the ECSW group (P=0.727).Conclusions:ECSW might affect PI3K-AKT activation,While there were no significant differences in the phosphorylation of ERK between the ECSW and the untreated group. The 0.09mJ/mm2 energy increased the expression of VEGF in HUVECs. MEK/ERK signal transduction pathway may play an important role in ECSW promoting the VEGF expression...