Thrombin activates NF-kappa B through thrombin receptor and results in proliferation of vascular smooth muscle cells: role of thrombin in atherosclerosis and restenosis
| Autor: | Syoko Ide, Hiroshi Shin, Koichiro Shigeta, Ikuro Maruyama, Toshihiro Nakajima, Isao Kitajima, Hironori Miyahara |
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| Rok vydání: | 1997 |
| Předmět: |
Vascular smooth muscle
Arteriosclerosis Thrombomodulin General Biochemistry Genetics and Molecular Biology Muscle Smooth Vascular chemistry.chemical_compound Thrombin History and Philosophy of Science Thrombin receptor medicine Humans biology General Neuroscience NF-kappa B NF-κB chemistry Mitogen-activated protein kinase Cancer research biology.protein Receptors Thrombin Signal transduction Tyrosine kinase Cell Division circulatory and respiratory physiology medicine.drug Signal Transduction |
| Zdroj: | Annals of the New York Academy of Sciences. 811 |
| ISSN: | 0077-8923 |
| Popis: | We investigated the role of thrombin in the pathogenesis in atherosclerosis and restenosis. First we examined the effect of thrombin on cultured human vascular smooth muscle cells (VSMC). We showed that thrombin acts as a mitogen on VSMC through thrombin receptor. The expression of thrombin receptor was increased in the cell lines of VSMC established from directional coronary atherectomy (DCA). This is more pronounced in the cells from patients with restenosis after PTCA. Next we investigated the signaling pathway from thrombin/thrombin receptor. Thrombin activates thrombin receptor resulting in the exposing of the agonist peptide domain (thrombin receptor agonist peptide, TRAP). The signal from thrombin/thrombin receptor activated protein C kinase, tyrosine kinase, and MAP kinase and resulted in NF-kappa B activation. Furthermore, treatment of the cells with antisense p65 oligodeoxynucleotides of NF-kappa B inhibited the thrombin-stimulated growth of VSMC in vitro. These results suggest that thrombin may have a role in the pathogenesis of atherosclerosis and restenosis after PTCA through the thrombin receptor. |
| Databáze: | OpenAIRE |
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