The potential mechanism for the effect of heparin on tissue plasminogen activator-mediated plasminogen activation

Jun F. Liang, Yongtao Li, Victor C. Yang

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The effects and possible role of heparin on tissue plasminogen activator-mediated plasminogen activation was thoroughly investigated. Direct analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that heparin increased the conversion of plasminogen to plasmin. Experiments by florescence quenching suggested that the stimulation of tissue plasminogen activator activity probably was due to a direct binding of heparin to tissue plasminogen activator, causing a conformational change of tissue plasminogen activator and rendering it more accessible to plasminogen interaction. The absence of additive stimulation effects on tissue plasminogen activator-mediated plasminogen activation when both heparin and fibrinogen were present also implied that both compounds interacted with tissue plasminogen activator via the same domain; it appeared to be most likely via the kringle-2 domain in tissue plasminogen activator based on studies using ε-aminocaproic acid as an inhibitor. Unlike heparin-induced stimulation of antithrombin-thrombin interaction, the heparin-induced stimulation of tissue plasminogen activator did not seem to follow a template model. Only in the presence of a high plasminogen or a low tissue plasminogen activator concentration, massive stimulation of tissue plasminogen activator activity was observed via a pseudotemplate model. The results suggest that precautions concerning high heparin dose should be given during its conjunctive clinical use with tissue plasminogen activator in thrombolytic therapy to reduce the risk of hemorrhage. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)349-358
Number of pages10
JournalThrombosis Research
Volume97
Issue number5
DOIs
StatePublished - 1 Mar 2000

Keywords

  • Fibrin(ogen)
  • Heparin stimulation
  • Plasminogen activation
  • Template-type stimulation
  • Tissue plasminogen activator

Fingerprint

Dive into the research topics of 'The potential mechanism for the effect of heparin on tissue plasminogen activator-mediated plasminogen activation'. Together they form a unique fingerprint.

Cite this