Induction of in vitro angiogenesis in the endothelial-derived cell line, EA hy926, by ethanol is mediated through PKC and MAPK

Biochem Biophys Res Commun. 1998 Aug 10;249(1):118-23. doi: 10.1006/bbrc.1998.9095.


We have previously shown that ethanol-induced injury to the gastric mucosa triggers increased expression of the angiogenic factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) and angiogenesis. To further investigate ethanol-induced angiogenesis, we used an in vitro angiogenesis model which employs the ability of an endothelial-derived cell line (EA hy926) to form tubelike structures resembling capillaries when plated on the matrix material, Matrigel. We report that serum-starved EA hy926 cells, incubated for as little as 5 minutes with ethanol concentrations of 1.0-2.5%, formed tubelike structures reflecting in vitro angiogenesis. Control cells, not incubated with ethanol, did not form tubelike structures. Incubation for 5 minutes with 2.5% ethanol resulted in increased activities of PKC and MAP kinase (ERK2) by 1.6-fold (p < 0.05) and 2.3-fold (P < 0.001), respectively. Furthermore, inhibitors of the MAPK kinase, MEK (PD98059) and PKC (GF 109203X) prevented the induction of in vitro angiogenesis by ethanol.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Line
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / physiology*
  • Enzyme Inhibitors / pharmacology
  • Ethanol / pharmacology*
  • Flavonoids / pharmacology
  • Humans
  • Indoles / pharmacology
  • MAP Kinase Kinase Kinase 1*
  • Maleimides / pharmacology
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / physiology*
  • Protein Kinase C / physiology*
  • Protein-Serine-Threonine Kinases / physiology*
  • Signal Transduction / drug effects


  • Enzyme Inhibitors
  • Flavonoids
  • Indoles
  • Maleimides
  • Ethanol
  • Protein-Serine-Threonine Kinases
  • Protein Kinase C
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human
  • bisindolylmaleimide I
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one