Coagulation-Associated Enhancement of Fibrinolytic Activity Via a Neutralization of PAI-1 Activity

Tetsumei Urano; Hayato Ihara; Yuko Suzuki; Yumiko Takada; Akikazu Takada

doi:10.1055/s-2000-9801

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2000; Volume 26(Number 01): 039-042
DOI: 10.1055/s-2000-9801

Coagulation-Associated Enhancement of Fibrinolytic Activity Via a Neutralization of PAI-1 Activity

Tetsumei Urano¹ , Hayato Ihara¹ , Yuko Suzuki¹ , Yumiko Takada² , Akikazu Takada¹

Supported in part by Grant-in Aid for Scientific Research nos. 09670041 and 10670040 from the Ministry of Education, Science and Culture, Japan. Department of
¹Physiology Hamamatsu University School of Medicine, Hamamatsu, Japan
²Department of Pathophysiology, Hamamatsu University School of Medicine, Hamamatsu, Japan

Abstract

ABSTRACT

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.

KEYWORD

PAI-1 - thrombin - factor Xa - vitronectin - fibrinolysis

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