The kinase inhibitor fasudil (HA-1077) reduces intimal hyperplasia through inhibiting migration and enhancing cell loss of vascular smooth muscle cells

作     者：Negoro, N Hoshiga, M Seto, M Kohbayashi, E Ii, M Fukui, R Shibata, N Nakakoji, T Nishiguchi, F Sasaki, Y Ishihara, T Ohsawa, N 

作者机构：Osaka Med Coll Dept Internal Med 1 Takatsuki Osaka 5698686 Japan Asahi Chem Ind Co Ltd Life Sci Res Ctr Frontier 21 Project Shizuoka 4160934 Japan 

出 版 物：《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》 (生物化学与生物物理学研究通讯)

年 卷 期：1999年第262卷第1期

页      面：211-215页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

主　　题：肌动蛋白类/代谢 主动脉 气囊扩张术 颈动脉损伤 细胞计数/药物作用 细胞分裂/药物作用 细胞运动/药物作用 细胞 培养的 剂量效应关系 药物 增生/病理学 微丝/药物作用 微丝/代谢 肌 平滑 血管/细胞学 肌 平滑 血管/药物作用 肌 平滑 血管/损伤 肌 平滑 血管/病理学 蛋白激酶抑制剂 时间因素 血管内膜/药物作用 血管内膜/损伤 血管内膜/病理学 伤口愈合/药物作用 动物 人类 男(雄)性 兔 

摘      要：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 antimigrative action of fasudil. In SMC (SM-3), fasudil (1-100 mu M) inhibited SMC migration in a dose-dependent man ner (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. (C) 1999 Academic Press.