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A variant of tissue plasminogen activator (t-PA) comprised of the Kringle 2 and the protease domain shows a significant difference in the in vitro rate of plasmin formation as compared to the recombinant human t-PA from transformed chinese hamster ovary cells

Fibrinolysis and Proteolysis
Publication Date
DOI: 10.1016/0268-9499(93)90060-9
  • Biology
  • Medicine


Abstract BM 06.022 is a tissue plasminogen activator (t-PA) variant comprised of the kringle 2 and the protease domain. In vivo data from animal studies provided evidence that BM 06.022 is a potent and fibrin specific fibrinolytic agent. In this study we present a detailed analysis of the in vitro rate of plasmin formation by BM 06.022. The activation of plasminogen by BM 06.022 was reduced as compared to CHO-t-PA when using CNBr-fragments of fibrinogen as a stimulator. However, a more detailed analysis revealed that the rate of plasmin formation by t-PA and BM 06.022 in the presence of CNBr-fragments of fibrinogen is dependent on the exact concentration of the stimulator because the activity-stimulator curves of both enzymes are non-parallel. In contrast, in the presence of fibrin-monomer and its plasmin derived degradation products the course of the activity-stimulator curve of BM 06.022 and t-PA was parallel. Furthermore, the concentrations of these stimulators which allowed 50% and maximal stimulation were very similar for BM 06.022 and CHO-t-PA. The rate of plasmin formation by BM 06.022 in the presence of fibrin-monomer and fibrin degradation products was lower by a factor of 2.0 and 4.3, respectively, as compared to CHO-t-PA. Furthermore, BM 06.022 and t-PA were not or only marginally stimulated by fibrinogen indicating that the systemic activation of fibrinolytic agents as it may occur during the therapy of the myocardial infarction may be due to a stimulation by fibrin degradation products rather than due to a stimulation by fibrinogen.

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