Human thrombin and calcium bound factor Xa significantly shorten tPA-induced fibrin clot lysis time via neutralization of plasminogen activator inhibitor type 1 activity.
Employing a fibrin clot lysis assay, we reassessed the significance of the neutralization of plasminogen activator inhibitor type 1 (PAI-1) activity by thrombin and factor-Xa in fibrinolysis. When PAI-1 enriched fibrin clots were formed using increasing concentrations of thrombin (0.1, 0.5, 1.0 IU/ml), their lysis times became shorter (43.8 +/- 4.9, 25.7 +/- 3.7, 13.9 +/- 0.8 h respectively). Times were shortened further by either heparin (43.9 +/- 11.0, 12.1 +/- 2.6, 3.6 +/- 0.2 h respectively) or vitronectin (17.0 +/- 1.6, 1.9 +/- 0.7, 0.9 +/- 0.0 h respectively). Factor-Xa together with Ca++ shortened the clot lysis time further. Fibrin autography revealed that both enzymes dose dependently interfered with complex formation between tPA and PAI-1, making large amounts of tPA remaining to be free form. The mechanism seems to play a role in the coagulation associated enhancement of fibrinolysis.
Urano
T
T
Department of Physiology, Hamamatsu University, School of Medicine, Shizuoka, Japan.
Nagai
N
N
Matsuura
M
M
Ihara
H
H
Takada
Y
Y
Takada
A
A
D000925:Anticoagulants / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D015951:Factor Xa / Q000378:metabolism / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008970:Molecular Weight; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012967:Sodium Dodecyl Sulfate; D013917:Thrombin / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D000925:Anticoagulants; D002135:Calcium-Binding Proteins; D017395:Plasminogen Activator Inhibitor 1; D012967:Sodium Dodecyl Sulfate; D006493:Heparin; D013917:Thrombin; D015951:Factor Xa; D010959:Tissue Plasminogen Activator