Hepatocyte growth factor is upregulated by low-density lipoproteins and inhibits endothelin-1 release

Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2865-71. doi: 10.1152/ajpheart.2000.279.6.H2865.

Abstract

Low-density lipoproteins (LDL) are known to cause endothelial injury and to promote the development of atherosclerotic lesions. This study demonstrates a significant concentration-dependent stimulatory effect of LDL on hepatocyte growth factor (HGF) synthesis (maximum release: 423 +/- 16% of control) and HGF receptor mRNA expression in cultured human coronary artery endothelial cells (HCAEC). HGF is a potent mitogen for endothelial cells but does not affect smooth muscle cell proliferation. In contrast, endothelin-1 (ET-1) acts as a mitogen on vascular smooth muscle cells and seems to be upregulated in coronary atherosclerosis. In this study, the basal ET-1 synthesis in HCAEC was concentration-dependently reduced by HGF (minimum: 54 +/- 3% of control). This inhibitory effect seems to be mediated via the tyrosine kinase activity of the HGF receptor c-met, since it was antagonized by the tyrosine kinase inhibitor lavendustin A. In addition, HGF also significantly reduced the LDL-stimulated ET-1 release. The LDL-induced upregulation of HGF synthesis in HCAEC and the inhibitory effect of HGF on ET-1 synthesis suggest a protective role of HGF in coronary atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / physiopathology
  • Coronary Vessels / cytology
  • Endothelin-1 / metabolism*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Hepatocyte Growth Factor / genetics*
  • Humans
  • Lipoproteins, LDL / pharmacology*
  • Proto-Oncogene Proteins c-met / genetics
  • RNA, Messenger / analysis

Substances

  • Endothelin-1
  • Lipoproteins, LDL
  • RNA, Messenger
  • oxidized low density lipoprotein
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met