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

 

PDF Download Buy Article Permissions and Reprints

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.

• References

• 1 Collen D. On the regulation and control of fibrinolysis. Thromb Haemostas 1980; 43: 77-89
  PubMedGoogle Scholar
• 2 Sakata Y, Aoki N. Cross-linking of a₂-plasmin inhibitor to fibrin by fibrin-stabilizing factor. J Clin Invest 1980; 65: 290-297
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 9 Krishnamurti C, Alving BM. Plasminogen activator inhibitor-1: biochemistry and evidence for modulation of fibrinolysis in vivo. Sem Thromb Hemostas, in press.
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 14 Knight LC, Budzynski AZ, Olexa SA. Radiolabelling of fibrinogen using the iodogen technique. Thromb Haemostas 1981; 46: 593-596
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 18 Masson-Lunven C, Angles-Cano E. PAI-1 and thrombotic risk: study of its interaction with fibrin. Fibrinolysis 1990; 4 (Supp) (13) 85
  PubMedGoogle Scholar
• 19 Noback C, Tinker JH. Hypothermia after cardiopulmonary bypass in man. Anesthesiology 1980; 53: 277-280
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 21 Reuler JB. Hypothermia: Pathophysiology, clinical settings and management. Ann Intern Med 1978; 89: 519-527
  CrossrefPubMedGoogle Scholar
• 22 Carr ME, Wolfert AL. Re warming by hemodialysis for hypothermia: failure of heparin to prevent DIC. J Emer Med 1988; 6: 277-280
  CrossrefPubMedGoogle Scholar