Palmitic acid promotes endothelial progenitor cells apoptosis via p38 and JNK mitogen-activated prot

• 作 者: Hai-long JIANG Mei LI Zong-gui WU Chun LIANG
• 机 构: Department of Cardiology,Second Hospital Affiliated to the Second Military Medical University,Shangh
• 出 处: 第五届国际络病学大会
• 发表日期: 2009年7期
• 关键词: Endothelial progenitor cells Palmitic acid Apoptosis Mitogen-activated protein k

Objective Recent studies have demonstrated that palmitic acid(PA) could regulate endothelial progenitor cells(EPCs) function(migration,proliferation,survival and angiogenesis) via various signal pathways,but the effect of PA on EPCs apoptosis and associated mechanisms are still elusive.Methods The human EPCs were oltained by Ficoll density gradient centrifugation and cultured in M199 medium containing rh-VEGF(30 ng/ml),rh-b-FGF(6 ng/ml) and 10％ fetal bovine serum for 7 days.The adhesive EPCs were harvested,then challenged with different concentrations of PA(ranging from 0 to 800 μmol/L) for 48 h and 400 μmol/L PA for different time periods(ranging from 0 to 60 h) after 12 h synchronization with serum free medium.The EPCs apoptosis was determined by flow cytometry,expression of caspase3,phosphorylated ERK1/2,JNK and p38 mitogen-activated protein kinase(MAPK) were quantified by Western-blot.The effect of PA on caspase-3 activity in the absence or presence of specific MAPK pathway inhibitors was determined by colorimetry.Results PA increased EPCs apoptosis in a dose-and time-dependent manner,upregulated phosphorylated p38 and JNK,caspase-3 expression of EPCs while ERK expression was not affected.PA induced EPCs apoptosis could be partly ameliorated by p38 inhibitor SB203580 and JNK inhibitor SP600125,but not by ERK1/2 inhibitor PD98059.Conclusion These findings suggested that PA promoted EPCs apoptosis via p38 and JNK MAPKs pathways.