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

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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

Further Information

Publication History

Publication Date:
31 December 2000 (online)

Abstract
Full Text
References

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

Crossref PubMed Search 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

PubMed Search 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

PubMed Search 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

Crossref PubMed Search 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

Search in Google Scholar
6 Loskutoff D J, Sawdey M, Mimuro J. Type 1 plasminogen activator inhibitor. Prog Hemost Thromb . 1989; 9 87-115

PubMed Search 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

PubMed Search 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

PubMed Search 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

Search 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

PubMed Search 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

Crossref PubMed Search 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

PubMed Search 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

PubMed Search 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

PubMed Search 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

PubMed Search 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

PubMed Search 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

PubMed Search 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

PubMed Search in Google Scholar