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

1  Institute of Clinical Chemistry and 2  Department of Microbiology, University Hospital Ulm, D-89070 Ulm, Germany Low-density lipoproteins (LDL) are known to cause endothelial injury and to promote the development of atherosclerotic lesions. This study demonstrates a significant concentration-depe...

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Published in:American journal of physiology. Heart and circulatory physiology 2000-12, Vol.279 (6), p.H2865-H2871
Main Authors: Haug, Cornelia, Schmid-Kotsas, Alexandra, Zorn, Ulrike, Bachem, Max G, Schuett, Sabine, Gruenert, Adolf, Rozdzinski, Eva
Format: Article
Language:English
Subjects:
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
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Summary:1  Institute of Clinical Chemistry and 2  Department of Microbiology, University Hospital Ulm, D-89070 Ulm, Germany 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. endothelin; endothelial cells
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.2000.279.6.h2865