Hirulog-1 reduces expression of platelet-derived growth factor in neointima of rat carotid artery induced by balloon catheter injury

Vascular restenosis is one of the major concerns for the treatment of ather osclerotic cardiovascular diseases using therapeutic vascular procedures. H irulog-1, a synthetic thrombin inhibitor, effectively reduced ischemic even ts in coronary heart disease patients and caused less hemorrhagic complicat ions compared to heparin. Thrombin stimulated the expression of platelet-de rived growth factor (PDGF) in vascular cells. PDGF receptor blockers reduce d angioplasty-induced restenosis in the swine model. The present study exam ined the effects of hirulog-1 on vascular stenosis, platelet deposition and the expression of PDGF in rat carotid arteries injured by balloon catheter . Multiple intravenous infusions of hirulog-1 (1 mg/kg/h for 4 h for 6 time s), but not bolus injection or 1-2 times of infusion, reduced neointima/med ia ratio by 50% in balloon-injured carotid arteries compared to injured ani mals receiving saline alone. Activated partial thromboplastin time in hirul og-1-treated rats was significantly prolonged compared to saline controls b ut shorter than that in animals receiving heparin (50 U/kg/h). One of hepar in-treated rat, but none of hirulog-1-treated, died from bleeding complicat ion. Hirulog-1 injection transiently reduced platelet deposition on denuded intima visualized by scanning electron microscopy. Abundance of PDGF in ne ointima of injured carotid arteries detected by immunohistochemistry was si gnificantly decreased following infusions of hirulog-1. The results suggest that balloon catheter injury induced neointima formation and the overexpre ssion of PDGF in the neointima of rat carotid artery may be effectively sup pressed by infusions with hirulog-1, a thrombin-specific inhibitor. Copyrig ht (C) 2000 S. Karger AG, Basel.