Hepatocyte growth factor is a survival factor for endothelial cells and is expressed in human atherosclerotic plaques

Harry Ma, Tina M. Calderon, John T. Fallon, Joan W. Berman

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Hepatocyte growth factor (HGF) has multiple effects on target cells upon activation of its receptor, c-Met. In endothelial cells, HGF induces migration, proliferation, and angiogenesis. HGF can also act as an anti-apoptotic factor for several cell types. The signal transduction pathways involved in mediating its anti-apoptotic effects have not been fully clarified. We demonstrated that HGF is anti-apoptotic for human endothelial cells, and identified the signaling pathways by which it mediates its effects. Human umbilical vein endothelial cells (HUVEC) exhibited significant levels of apoptosis after serum deprivation. HGF inhibited apoptosis in a dose dependent manner in serum-deprived cultures. HGF induced the phosphorylation of Akt and Erk1/2, cell survival factors, in a time dependent manner in serum deprived HUVEC. Inhibition of Akt and Erk1/2 activation abolished the anti-apoptotic effects of HGF. The transcription factor, NF-κB, can also play a role in promoting cell survival. However, NF-κB does not appear to contribute to the anti-apoptotic properties of HGF, as nuclear translocation of NF-κB was not detected in HGF-treated cultures. Endothelial cell migration, proliferation, and apoptosis contribute to the pathogenesis of atherosclerosis, and HGF may play a role in the development and progression of vascular lesions. Immunohistochemical analysis of human carotid artery sections demonstrated HGF protein localization within atherosclerotic lesions but not in normal vessels, suggesting that HGF may participate in atherogenesis.

Original languageEnglish (US)
Pages (from-to)79-87
Number of pages9
JournalAtherosclerosis
Volume164
Issue number1
DOIs
StatePublished - Jul 24 2002

Keywords

  • Apoptosis
  • Atherosclerosis
  • Endothelium
  • Hepatocyte growth factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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