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

Smooth muscle cell (SMC) migration plays an important role in restenosis af ter angioplasty, Myosin phosphorylation is necessary for cell migration. Fa sudil is an inhibitor of protein kinases, including myosin light chain kina se and Rho associated kinase, thereby inhibiting myosin phosphorylation, an d it has been clinically used to prevent vasospasm following subarachnoid h emorrage, 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 d ose-dependent man ner (p < 0,001), Fasudil suppressed actin stress fiber fo rmation 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 enhance d cell loss in the media after injury. We concluded that fasudil reduced ne ointimal formation after balloon injury through both inhibiting migration a nd enhancing cell loss of medial SMC. (C) 1999 Academic Press.