Antithrombotic activity of a monoclonal antibody inducing the substrate form of plasminogen activator inhibitor type 1 in rat models of venous and arterial thrombosis

摘要

Elevated plasminogen activator inhibitor 1 (PAI-1) is a risk factor for thrombosis, and inhibitors of the interaction between PAI-1 and tissue plasminogen activator (t-PA) have antithrombotic and pro- thrombolytic activity in animals. We describe the antithrombotic effects in the rat of a monoclonal antibody(MA33H1) which converts PAI-1 to a non-inhibitory substrate. The activity of MA33H1 against rat PAI-1 was confirmed using two-chain t-PA and a chromogenic Substrate. MA33H1 was evaluated in rat venous (thromboplastin + stasis in the abdominal vena cava) And arterial (electric current applied to a carotid artery) thrombosis models. the effects on tail- Transection bleeding time were studied.