Coagulation-associated enhancement of fibrinolytic activity via a neutralization of PAI-1 activity.
Total fibrinolytic activity in the vasculature is finely tuned by the balance between tissue plasminogen activator and plasminogen activator inhibitor type 1 (PAI-1). Although PAI-1 targets plasminogen activators, it also reacts with other serine proteases such as thrombin and factor Xa. The latter was shown to interact with PAI-1 only when a physiological concentration of calcium ions (Ca++) is present. Through such interaction, thrombin and Ca++-bound factor Xa shortened fibrin clot lysis times in a purified system by neutralizing PAI-1 activity. Both unfractionated heparin and vitronectin were shown to enhance the clot lysis further. Together with the cleavage and inactivation of PAI-1 by human neutrophil elastase, which was reported previously from our laboratory, such neutralization of PAI-1 activity by these serine proteases was shown to be strongly involved in the coagulation-associated enhancement of fibrinolytic activity.
Urano
T
T
Department of Physiology, Hamamatsu University School of Medicine, Japan. uranot@hama-med.ac.jp
Ihara
H
H
Suzuki
Y
Y
Takada
Y
Y
Takada
A
A
D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D015951:Factor Xa / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology*; D012697:Serine Endopeptidases / Q000097:blood; D013917:Thrombin / Q000502:physiology; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D019096:Vitronectin / Q000494:pharmacology
D000925:Anticoagulants; D017395:Plasminogen Activator Inhibitor 1; D019096:Vitronectin; D010958:Plasminogen; D006493:Heparin; D012697:Serine Endopeptidases; D019272:Leukocyte Elastase; D013917:Thrombin; D015951:Factor Xa; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D002118:Calcium