The Kinase Inhibitor Fasudil (HA-1077) Reduces Intimal Hyperplasia through Inhibiting Migration and Enhancing Cell Loss of Vascular Smooth Muscle Cells
| Autor: | Nobuyuki Negoro, Masaaki Hoshiga, Minoru Seto, Eiko Kohbayashi, Masaaki Ii, Ryosuke Fukui, Nobuhiko Shibata, Takahiro Nakakoji, Futoshi Nishiguchi, Yasuharu Sasaki, Tadashi Ishihara, Nakaaki Ohsawa |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Time Factors Stress fiber Intimal hyperplasia Myosin light-chain kinase Vascular smooth muscle Biophysics Cell Count Pharmacology Biochemistry Muscle Smooth Vascular Catheterization Cell Movement 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine medicine Animals Humans Protein Kinase Inhibitors Molecular Biology Aorta Cells Cultured Wound Healing Hyperplasia Dose-Response Relationship Drug Kinase Chemistry Fasudil Cell migration Cell Biology Anatomy medicine.disease Actin cytoskeleton Actins Actin Cytoskeleton Rabbits Carotid Artery Injuries Tunica Intima Cell Division |
| Zdroj: | Biochemical and Biophysical Research Communications. 262:211-215 |
| ISSN: | 0006-291X |
| Popis: | Smooth muscle cell (SMC) migration plays an important role in restenosis after angioplasty. Myosin phosphorylation is necessary for cell migration. Fasudil is an inhibitor of protein kinases, including myosin light chain kinase and Rho associated kinase, thereby inhibiting myosin phosphorylation, and it has been clinically used to prevent vasospasm following subarachnoid hemorrage. Based on these findings, we examined the anti-migrative action of fasudil. In SMC (SM-3), fasudil (1-100 microM) inhibited SMC migration in a dose-dependent manner (p < 0.001). Fasudil suppressed actin stress fiber formation dose dependently. In rabbit carotid artery, fasudil (10 mg/kg/day) markedly reduced intimal hyperplasia 14 days following balloon injury. Cell kinetic study showed that fasudil did not affect proliferation but enhanced cell loss in the media after injury. We concluded that fasudil reduced neointimal formation after balloon injury through both inhibiting migration and enhancing cell loss of medial SMC. |
| Databáze: | OpenAIRE |
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