Hepatocyte growth factor is upregulated by low-density lipoproteins and inhibits endothelin-1 release
| Autor: | Max G. Bachem, Cornelia Haug, Adolf Gruenert, Sabine Schuett, Ulrike Zorn, Alexandra Schmid-Kotsas, Eva Rozdzinski |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Vascular smooth muscle Physiology Gene Expression Coronary Artery Disease Biology Downregulation and upregulation Physiology (medical) Internal medicine medicine Humans RNA Messenger Cells Cultured Endothelin-1 Cell growth Hepatocyte Growth Factor Proto-Oncogene Proteins c-met Endothelin 1 Coronary Vessels Endothelial stem cell Lipoproteins LDL Endocrinology Hepatocyte growth factor Endothelium Vascular Cardiology and Cardiovascular Medicine Endothelin receptor Tyrosine kinase medicine.drug |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 279(6) |
| ISSN: | 0363-6135 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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