Skip to main content
SpringerLink
Log in
Book cover

Biomedical Aspects of Drug Targeting pp 85–106Cite as

Thrombus Targeting of Plasminogen Activators and Anticoagulants

  • Chapter

  • 300 Accesses

Abstract

Large-scale studies with mortality endpoints comparing fibrinolytic therapy with placebo in patients with acute myocardial infarction (AMI) have documented the benefit of timely dissolution of coronary arterial thrombi by intravenous infusion of plasminogen activators (Fig. 1).(1)

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Armstrong PW, Collen D (2001) Fibrinolysis for acute myocardial infarction: Current status and new horizons for pharmacological reperfusion, Circulation 103: 2862–66

    Google Scholar 

  2. The GUSTO Angiographic Investigators (1993) The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 329:1615— 1622

    Google Scholar 

  3. Bode C, Smalling RW. Berg O, Burnett C, Lorch O, Kalbfleisch JM, Chernoff R, Christie LG, Feldman RL, Seals AA. Weaver WD. for the RAPID II Investigators (1996) Randomized comparison of coronary thrombolysis achieved with double-bolus reteplase (recombinant plasminogen activator) and front-loaded, accelerated alteplase (recombinant tissue plasminogen activator) in patients with acute myocardial infarction. Circulation 94:891–898

    Article  Google Scholar 

  4. Assessment of the Safety and Efficacy of a New Thrombolytic Investigators (1999) Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomized trial. Lancet 354: 716–22

    Google Scholar 

  5. The GUSTO V Investigators (2001) Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomized trial. Lancet 357: 1905–1914

    Article  Google Scholar 

  6. Hui KY, Haber E, Matsueda GR (1983) Monoclonal antibodies to a synthetic fibrin-like peptide bind to human fibrin but not fibrinogen. Science 222:1129— 113211.

    Article  Google Scholar 

  7. Califf RM (2000) Combination therapy for acute myocardial infarction: fibrinolytic therapy and glycoprotein IIb/IIIa inhibition. Am Heart J 139 Suppl: S33 — S37

    Article  Google Scholar 

  8. Topol EJ, Byzova TV, Plow EF (1999) Platelet GPIIb-IIIa blockers. Lancet 353: 227–31

    Article  Google Scholar 

  9. Smith JW, Tachias K, Madison EL (1995) Protein loop grafting to construct a variant of tissue-type plasminogen activator that binds platelet integrin allbß3. J Biol Chem 270: 30486–30490

    Article  Google Scholar 

  10. Bode C, Matsueda GR, Hui KY, Haber E (1985) Antibody-directed urokinase: a specific fibrinolytic agent. Science 229: 765–767

    Article  Google Scholar 

  11. Runge MS, Bode C, Matsueda GR, Haber E (1988) Conjugation to an antifibrin monoclonal antibody enhances the fibrinolytic potency of tissue plasminogen activator in vitro. Biochemistry 27: 1153–1157

    Article  Google Scholar 

  12. Runge MS, Bode C, Matsueda GR, Haber E (1987) Antibody-enhanced thrombolysis: Targeting of tissue plasminogen activator in vivo. Proc Natl Acad Sci USA 84: 7659–7662

    Article  Google Scholar 

  13. Bode C, Runge MS. Schönermark S, Eberle T, Newell JB. Kübler W. Haber E (1990) Conjugation to antifibrin Fab’ enhances fibrinolytic potency of single-chain urokinase plasminogen activator. Circulation 81:1974–1980

    Article  Google Scholar 

  14. Bode C, Meinhardt G, Runge MS, Freitag M, Nordt T. Arens M. Newell JB, Kübler W. Haber E (1991) Platelet-targeted fibrinolysis enhances clot lysis and inhibits platelet aggregation. Circulation 84: 805–813

    Article  Google Scholar 

  15. Dewerchin M, Lijnen HR. Stassen JM. De Cock F, Quertermous T, Ginsberg MH, Piow EF, Collen D (1991) Effect of chemical conjugation of recombinant single-chain urokinase-type plasminogen activator with monoclonal antiplatelet antibodies on platelet aggregation and on plasma clot lysis in vitro and in vivo. Blood 78: 1005–1018

    Google Scholar 

  16. Bode C, Runge MS. Branscomb EE, Newell JB. Matsueda GR. Haber E (1989) Antibody-directed fibrinolysis. An antibody specific for both fibrin and tissue plasminogen activator. J Biol Chem 264: 944–948

    Google Scholar 

  17. Ruef J, Nordt TK, Peter K, Runge MS, Kübler W, Bode C (1999) A bispecific antifibrin-antiplatelet urokinase conjugate ( BAAUC) induces enhanced clot lysis and inhibits platelet aggregation. Thromb Haemost 82: 109–114

    Google Scholar 

  18. Charpie JR, Runge MS, Matsueda GR, Haber E (1990) A bispecific antibody enhances the fibrinolytic potency of single-chain urokinase. Biochemistry 29: 6374–6378

    Article  Google Scholar 

  19. Runge MS, Bode C, Savard CE. Matsueda GR, Haber E (1990) Antibody-directed fibrinolysis: a bispecific (Fab`)2 that binds to fibrin and tissue plasminogen activator. Bioconjug Chem 1: 274–277

    Article  Google Scholar 

  20. Branscomb EE, Runge MS, Savard CE. Adams KM, Matsueda GR. Haber E (1990) Bispecific monoclonal antibodies produced by somatic cell fusion increase the potency of tissue plasminogen activator. Thromb Haemost 64: 260–266

    Google Scholar 

  21. Goldstein J, Matsueda GR, Shaw S-Y (1996) A chimenic streptokinase with unexpected fibrinolytic selectivity. Thromb Haemost 76: 429–438

    Google Scholar 

  22. Schnee JM, Runge MS. Matsueda GR, Hudson NW, Seidman JG, Haber E, Quertermous T (1987) Construction and expression of a recombinant antibody-targeted plasminogen activator. Proc Natl Acad Sci USA 84: 6904–6908

    Article  Google Scholar 

  23. Love TW, Quertermous T, Runge MS, Michelson KD, Matsueda GR, Haber E (1994) Attachment of an antifibrin antibody to the amino terminus of tissue-type plasminogen activator impairs stimulation by fibrin. Fibrinolysis 8: 326–332

    Google Scholar 

  24. Runge MS, Quertermous T, Zavodny PJ, Love TW, Bode C. Freitag M, Shaw S-Y, Huang PL. Chou C-C, Mullins D, Schnee JM, Savard CE, Rothenberg ME, Newell JB, Matsueda GR. Haber E (1991) A recombinant chimeric plasminogen activator with high affinity for fibrin has increased thrombolytic potency in vitro and in vivo. Proc Nat Acad Sci USA 88: 10337–10341

    Article  Google Scholar 

  25. Runge MS, Harker LA, Bode C, Ruef J, Kelly AB. Marzec UM; Allen E. Caban R, Shaw S-Y, Haber E. Hanson SR (1996) Enhanced thrombolytic and antithrombotic potency of a fibrin-targeted plasminogen activator in baboons. Circulation 94:14121–422

    Article  Google Scholar 

  26. Peter K, Tovic I, Graeber J, Weirich U, Bauer S, Ruef J, Nordt T, Bode C (2001) Construction and functional evaluation of a new fibrin-targeted fibrinolytic: a recombinant fusion protein with an anti-fibrin single-chain antibody and a low molecular weight form single-chain urokinase. Circulation 104:SII-96

    Google Scholar 

  27. Dewerchin M, Vandamme AM. Holvoet P, De Cock F, Lemmens G. Lijnen HR. Stassen JM. Gollen D (1992) Thrombolytic and pharmacokinetic properties of a recombinant chimeric plasminogen activator consisting of a fibrin fragment D-dimer specific humanized monoclonal antibody and a truncated single-chain urokinase. Thromb Haemost 68:170–179

    Google Scholar 

  28. Holvoet P, Laroche Y, Stassen JM, Lijnen HR, Van Hoef B, De Cock F, Van Houtven A, Gansemans Y, Matthyssens G, Collen D (1993) Pharmacokinetic and thrombolytic properties of chimeric plasminogen activators consisting of a single-chain Fv fragment of a fibrin-specific antibody fused to single-chain urokinase. Blood 81: 696–703

    Google Scholar 

  29. Yang W-P. Goldstein J, Procyk R, Matsueda GR. Shaw S-Y (1994) Design and evaluation of a thrombin-activable plasminogen activator. Biochemistry 33: 2306–2312

    Google Scholar 

  30. Yamada T, Shimada Y. Kikuchi M (1996) Integrin-specific tissue-type plasminogen activator engineered by introduction of the Arg-Gly-Asp sequence. Biochem Biophys Res Commun 228: 306–311

    Article  Google Scholar 

  31. Dawson KM, Cook A, Devine JM. Edwards RM, Hunter MG. Raper RH. Roberts G (1994) Plasminogen mutants activated by thrombin. Potential thrombus-selective thrombolytic agents. J Biol Chem 269: 15989–15992

    Google Scholar 

  32. Wan H, Liu Z. Xia X, Gu J, Wang B. Liu X. Zhu M. Li P, Ruan C (2000) A recombinant antibody-targeted plasminogen activator with high affinity for activated platelets increases thrombolytic potency in vitro and in vivo. Thromb Res 97: 133–141

    Article  Google Scholar 

  33. Hua Z-C, Chen X-C, Dong C, Zhu D-X (1996) Characterization of a recombinant chimeric plasminogen activator composed of Gly-Pro-Arg-Pro tetrapeptide and truncated urokinase-type plasminogen activator expressed in Escherichia coli. Biochem Biophys Res Commun 222: 576–583

    Article  Google Scholar 

  34. Tait JF, Engelhardt S, Smith C, Fujikawa K (1995) Prourokinase-annexin V chimeras. Construction, expression, and characterization of recombinant proteins. J Biol Chem 270: 21594–21599

    Article  Google Scholar 

  35. van Zvl WB. Pretorius GHJ. Hartmann M. Kotze HF (1997) Production of a recombinant antithrombotic and fibrinolytic protein, PLATSAK, in Escherichia coli. Thromb Res88: 419–426

    Article  Google Scholar 

  36. Bode C, Hudelmayer M, Mehwald P, Bauer S, Freitag M, von Hodenberg E. Newell JB, Kübler W, Haber E, Runge MS (1994) Fibrin-targeted recombinant hirudin inhibits fibrin deposition on experimental clots more efficiently than recombinant hirudin. Circulation 90: 1956–1963

    Article  Google Scholar 

  37. Bode C, Hanson SR, Schmedtje JF Jr. Haber E, Mehwald P, Kelly AB. Harker LA, Runge MS (1997) Antithrombotic potency of hirudin is increased in nonhuman primates by fibrin targeting. Circulation 95:800–804

    Article  Google Scholar 

  38. Peter K, Graeber J, Kipriyanov S, Zewe-Welschof M, Runge MS, Kibler W, Little M, Bode C (2000) Construction and functional evaluation of a single-chain antibody fusion protein with fibrin targeting and thrombin inhibition after activation by factor Xa. Circulation 101: 1158–1164

    Article  Google Scholar 

  39. Muzykantov VR, Barnathan ES, Atochina EN, Kuo A, Danilov SM, Fisher AB (1996) Targeting of antibody-conjugated plasminogen activators to the pulmonary vasculature. J Pharmacol Exp Ther 279: 1026–1034

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology and Angiology, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany

    Karlheinz Peter & Christoph Bode

Authors
  1. Karlheinz Peter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christoph Bode
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Vladimir Muzykantov M.D., Ph.D.

  2. School of Pharmacy, Northeastern University, Boston, MA, USA

    Vladimir Torchilin Ph.D., D.Sc.

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media New York

About this chapter

Cite this chapter

Peter, K., Bode, C. (2002). Thrombus Targeting of Plasminogen Activators and Anticoagulants. In: Muzykantov, V., Torchilin, V. (eds) Biomedical Aspects of Drug Targeting. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-4627-3_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-4627-3_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-5312-4

  • Online ISBN: 978-1-4757-4627-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation