Effect of Plasminogen Activator Inhibitor-1 on Tissue-Type Plasminogen Activator-Induced Fibrinolysis

Marcus E Carr Jr.; C Krishnamurti; B M Alving

doi:10.1055/s-0038-1648389

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1992; 67(01): 106-110
DOI: 10.1055/s-0038-1648389

Original Articles

Schattauer GmbH Stuttgart

Effect of Plasminogen Activator Inhibitor-1 on Tissue-Type Plasminogen Activator-Induced Fibrinolysis

Marcus E Carr Jr.

¹The Medical Service, McGuire Veterans Administration Hospital, the Departments of Internal Medicine and Pathology, Medical College of Virginia, Richmond, VA, USA

,

C Krishnamurti

²The Division of Medicine, Hematology Branch, Walter Reed Army Institute of Research, Washington, D. C., USA

,

B M Alving

²The Division of Medicine, Hematology Branch, Walter Reed Army Institute of Research, Washington, D. C., USA

› Author Affiliations

Abstract

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Summary

The effect of fibrin on the interaction of human recombinant single-chain tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) was studied in normal rabbit plasma and in plasma with high levels of native PAI-1. t-PA was added to diluted plasma containing calcium (10 mM) and ¹²⁵I-fibrinogen at 37° C. Clotting was initiated with human thrombin, and lysis was monitored both turbidimetrically and by release of ¹²⁵I-fibrin degradation products (fdp). The activity of t-PA (50 IU/ml) was rapidly reduced to 15% of the initial value in plasma containing PAI-1 (23 AU/ml). When thrombin and t-PA were added simultaneously to the plasma, more than 70% of the activity was retained through incorporation of t-PA into the fibrin clot. t-PA-induced fibrinolysis in PAI-1 enriched plasma was further delayed when the temperature was reduced from 37 to 25° C. Turbidimet-ric and ¹²⁵I-fdp release data provided complementary information. The former technique traced fiber dissolution, while the latter reflected network integrity. These results indicate that t-PA-induced fibrinolysis in PAI-1 enriched plasma is modulated by the presence of fibrin and by temperature.

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References

References
1 Collen D. On the regulation and control of fibrinolysis. Thromb Haemostas 1980; 43: 77-89
2 Sakata Y, Aoki N. Cross-linking of a₂-plasmin inhibitor to fibrin by fibrin-stabilizing factor. J Clin Invest 1980; 65: 290-297
3 Loskutoff DJ, van Mourik JA, Erickson LA, Lawrence D. Detection of an unusually stable fibrinolytic inhibitor produced by bovine endothelial cells. Proc Natl Acad Sci USA 1983; 80: 2956-2960
4 Fay WP, Owen WG. Platelet plasminogen activator inhibitor purification and characterization of interaction with plasminogen activators and activated protein C. Biochemistry 1989; 28: 5773-5778
5 Chimielewska J, Ranby M, Wiman B. Kinetics of the inhibition of plasminogen activators by the plasminogen-activator inhibitor. Biochem J 1988; 25: 327-332
6 Colucci M, Paramo JA, Collen D. Generation in plasma of a fastacting inhibitor of plasminogen activator in response to endotoxin stimulation. J Clin Invest 1985; 75: 818-824
7 Krishnamurti C, Barr CF, Hassett MA, Young GD, Alving BM. Plasminogen activator inhibitor: a regulator of ancrod-induced fibrin deposition in rabbits. Blood 1987; 69: 798-803
8 Krishnamurti C, Young GD, Colleton CA, Alving BM. Enhancement of tissue plasminogen activator-induced fibrinolysis by activated protein C in endotoxin-treated rabbits. J Lab Clin Med 1991; 118: 523-530
9 Krishnamurti C, Alving BM. Plasminogen activator inhibitor-1: biochemistry and evidence for modulation of fibrinolysis in vivo. Sem Thromb Hemostas, in press.
10 Erickson LA, Fici GJ, Lund JE, Boyle TP, Polites GH, Marotti KR. Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene. Nature 1990; 346: 74-76
11 Wagner OF, de Vries C, Hohmann C, Veerman H, Pannekoek H. Interaction between plasminogen activator inhibitor type 1 (PAI-1) bound to fibrin and either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA). J Clin Invest 1989; 84: 647-655
12 Colucci M, Paramo JA, Collen D. Inhibition of one-chain and two-chain forms of human tissue-type plasminogen activator by the fastacting inhibitor of plasminogen activator in vitro and in vivo. J Lab Clin Med 1986; 108: 53-59
13 Kazal LA, Amsel S, Miller OP, Tocantins LM. The preparation and some properties of fibrinogen precipitated from human plasma by glycine. Proc Soc Exp Biol Med 1963; 113: 989-994
14 Knight LC, Budzynski AZ, Olexa SA. Radiolabelling of fibrinogen using the iodogen technique. Thromb Haemostas 1981; 46: 593-596
15 Carr ME, Gabriel DA. The effect of dextran 70 on the structure of plasma-derived fibrin gels. J Lab Clin Med 1980; 96: 985-993
16 Wilhelm OG, Jaskunas SR, Vlahos CJ, Bang NU. Functional properties of the Kringle-1 and Kringle-2 domains of tissue-type plasminogen activator produced in E. coli.. Fibrinolysis 1990; 4 (Supp) (13) 94
17 Salonen EM, Vaheri A, Pollanen J, Stephens R, Andreasen P, Mayer M, Dano K, Gailit J, Ruoslahti E. Interaction of plasminogen activator inhibitor (PAI-1) with vitronectin. J Biol Chem 1989; 264: 6339-6343
18 Masson-Lunven C, Angles-Cano E. PAI-1 and thrombotic risk: study of its interaction with fibrin. Fibrinolysis 1990; 4 (Supp) (13) 85
19 Noback C, Tinker JH. Hypothermia after cardiopulmonary bypass in man. Anesthesiology 1980; 53: 277-280
20 Nieminen MT, Rosow CE, Triantafillou A, Scheider RC, Lowenstein E, Philbin DM. Temperature gradients in cardiac surgical patients - a comparison of halothane and fentanyl. Anesth Analg 1983; 62: 1002-1005
21 Reuler JB. Hypothermia: Pathophysiology, clinical settings and management. Ann Intern Med 1978; 89: 519-527
22 Carr ME, Wolfert AL. Re warming by hemodialysis for hypothermia: failure of heparin to prevent DIC. J Emer Med 1988; 6: 277-280