Administration of pigment epithelium-derived factor prolongs bleeding time by suppressing plasminogen activator inhibitor-1 activity and platelet aggregation in rats.

We have recently found that pigment epithelium-derived factor (PEDF), a glycoprotein with potent neuronal differentiating activity, not only inhibits endothelial cell damage, smooth muscle cell proliferation and platelet aggregation in vitro, but also suppresses occlusive thrombus formation in rats. These observations suggest PEDF may play a protective role against atherothrombosis. However, effects of PEDF on hemostasis, fibrinolysis and platelet function in vivo are not fully understood. In this study, we examined the effects of PEDF on tail vein bleeding time, plasminogen activator inhibitor-1 (PAI-1) activity and ex vivo-platelet aggregation in rats. Intravenous injection of 30 microg PEDF significantly prolonged the tail vein bleeding time by about 25%. Administration of 30 microg PEDF was also found to reduce the PAI-1 activity in rats. Further, ADP-induced platelet aggregation was suppressed in PEDF-treated rats. The present study demonstrated first that PEDF exerted anti-hemostatic effects in rats, at least in part by suppressing PAI-1 activity and platelet aggregation. PEDF may be a novel therapeutic target for the treatment of patients with thrombogenic tendency and hypercoagulability.