Semin Thromb Hemost 2000; Volume 26(Number 01): 039-042
DOI: 10.1055/s-2000-9801
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4663)

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
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
31. Dezember 2000 (online)

 

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

REFERENCES

  • 1 Castellino F J. Recent advances in the chemistry of the fibrinolytic system.  Chem Rev . 1981;  81 431-446
    CrossrefPubMedSuche in Google Scholar
  • 2 Urano T, de Serrano V S, Chibber B A, Castellino F J. The control of the urokinase-catalyzed activation of human glutamic acid 1-plasminogen by positive and negative effectors.  J Biol Chem . 1987;  262 15959-15964
    PubMedSuche in Google Scholar
  • 3 Hoylaerts M, Rijken D C, Lijnen H R, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin.  J Biol Chem . 1982;  257 2912-2919
    PubMedSuche in Google Scholar
  • 4 Sakata Y, Aoki N. Cross-linking of alpha 2-plasmin inhibitor to fibrin by fibrin-stabilizing factor.  J Clin Invest . 1980;  65 290-297
    CrossrefPubMedSuche in Google Scholar
  • 5 Castellino F J. Plasminogen. In: High KA, Roberts HR, eds. Molecular Basis of Thrombosis and Hemostasis New York, NY: Marcel Dekker 1995: 495-515
    Suche in Google Scholar
  • 6 Loskutoff D J, Sawdey M, Mimuro J. Type 1 plasminogen activator inhibitor.  Prog Hemost Thromb . 1989;  9 87-115
    PubMedSuche in Google Scholar
  • 7 Urano T, Sakakibara K, Rydzewski A. Relationships between euglobulin clot lysis time and the plasma levels of tissue plasminogen activator and plasminogen activator inhibitor 1.  Thromb Haemost . 1990;  63 82-86
    PubMedSuche in Google Scholar
  • 8 Urano T, Sumiyoshi K, Pietraszek M H, Takada Y, Takada A. PAI-1 plays an important role in the expression of t-PA activity in the euglobulin clot lysis by controlling the concentration of free t-PA.  Thromb Haemost . 1991;  66 474-478
    PubMedSuche in Google Scholar
  • 9 Stack M S, Madison E L, Pizzo S V. Tissue-type plasminogen activator. In: High KA, Roberts HR, eds. Molecular Basis of Thrombosis and Hemostasis New York, NY: Marcel Dekker 1995: 479-494
    Suche in Google Scholar
  • 10 Wallén P, Bergsdorf N, Rånby M. Purification and identification of two structural variants of porcine tissue plasminogen activator by affinity adsorption on fibrin.  Biochim Biophys Acta . 1982;  719 318-328
    PubMedSuche in Google Scholar
  • 11 Carrell R W, Evans D L, Stein P E. Mobile reactive centre of serpins and the control of thrombosis.  Nature . 1991;  353 576-578
    CrossrefPubMedSuche in Google Scholar
  • 12 Berrettini M, Schleef R R, Espana F, Loskutoff D J, Griffin J H. Interaction of type 1 plasminogen activator inhibitor with the enzymes of the contact activation system.  J Biol Chem . 1989;  264 11738-11743
    PubMedSuche in Google Scholar
  • 13 Ehrlich H J, Gebbink R K, Keijer J. Alteration of serpin specificity by a protein cofactor. Vitronectin endows plasminogen activator inhibitor 1 with thrombin inhibitory properties.  J Biol Chem . 1990;  265 13029-13035
    PubMedSuche in Google Scholar
  • 14 Keijer J, Linders M, Wegman J J. On the target specificity of plasminogen activator inhibitor 1: the role of heparin, vitronectin, and the reactive site.  Blood . 1991;  78 1254-1261
    PubMedSuche in Google Scholar
  • 15 Urano T, Ihara H, Takada Y, Nagai N, Takada A. The inhibition of human factor Xa by plasminogen activator inhibitor type 1 in the presence of calcium ions, and its enhancement by heparin and vitronectin.  Biochim Biophys Acta . 1996;  1298 199-208
    PubMedSuche in Google Scholar
  • 16 Sakata Y, Loskutoff D J, Gladson C L, Hekman C M, Griffin J H. Mechanism of protein C-dependent clot lysis: role of plasminogen activator inhibitor.  Blood . 1986;  68 1218-1223
    PubMedSuche in Google Scholar
  • 17 Urano T, Nagai N, Matsuura M. Human thrombin and calcium bound factor Xa significantly shorten t-PA-induced fibrin clot lysis time via neutralization of plasminogen activator inhibitor type 1 activity.  Thromb Haemost . 1998;  80 161-166
    PubMedSuche in Google Scholar
  • 18 Wu K, Urano T, Ihara H. The cleavage and inactivation of plasminogen activator inhibitor type 1 by neutrophil elastase: The evaluation of its physiologic relevance in fibrinolysis.  Blood . 1995;  86 1056-1061
    PubMedSuche in Google Scholar