Palmitic acid promotes endothelial progenitor cells apoptosis via p38 and JNK mitogen-activated protein kinase pathways

Atherosclerosis. 2010 May;210(1):71-7. doi: 10.1016/j.atherosclerosis.2009.10.032. Epub 2009 Nov 5.


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 obtained by Ficoll density gradient centrifugation and cultured in M199 medium containing rh-VEGF (30ng/mL), rh-b-FGF (6ng/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 800mumol/L) for 48h and 400 micromol/L PA for different time periods (ranging from 0 to 60h) after 12h synchronization with serum-free medium. The EPCs apoptosis was determined by flow cytometry, expression of caspase-3, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology
  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cells, Cultured
  • Endothelial Cells / enzymology
  • Endothelial Cells / physiology*
  • Flavonoids / pharmacology
  • Flow Cytometry
  • Humans
  • Imidazoles / pharmacology
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Palmitic Acid / pharmacology*
  • Pyridines / pharmacology
  • Stem Cells / enzymology
  • Stem Cells / physiology
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Anthracenes
  • Flavonoids
  • Imidazoles
  • Pyridines
  • pyrazolanthrone
  • Palmitic Acid
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one