New derivative of staphylokinase SAK-RGD-K2-Hirul exerts thrombolytic effects in the arterial thrombosis model in rats
Comparative study published in Pharmacological reports : PR (2011)
Abstract
SAK-RGD-K2-Hir and SAK-RGD-K2-Hirul are recombinant proteins that are derivatives of r-SAK (recombinant staphylokinase). They are characterized by their fibrin-specific plasminogen activation properties and their antithrombin and antiplatelet activities. The difference between these proteins is the presence of the antithrombotic fragment (hirudin or hirulog) in the C-terminal portion of the r-SAK. The aim of the present study was to examine the thrombolytic potentials of SAK-RGD-K2-Hir and SAK-RGD-K2-Hirul in an electrically induced carotid artery thrombosis model in rats and to compare the potentials to that of r-SAK. We determined that a bolus injection of SAK-RGD-K2-Hirul was more effective than one of r-SAK in the improvement and maintenance of carotid patency and in arterial thrombus weight reduction; however, it had the same potency as SAK-RGD-K2-Hir. The bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in the animals that were treated with either dose (1.5 or 3.0 mg/kg) of SAK-RGD-K2-Hir or SAK-RGD-K2-Hirul, whereas no changes were observed in the plasma fibrinogen concentration or the α2 plasmin inhibitor level. r-SAK alone did not change the bleeding time or coagulation parameters. In conclusion, our findings demonstrate the thrombolytic activity of intravenous bolus injection of the novel thrombolytic agent SAK-RGD-K2-Hirul in rats. Although this protein compares favorably with r-SAK, we were unable to show the presence of any beneficial effects of SAK-RGD-K2-Hirul over those of SAK-RGD-K2-Hir. Furthermore, our results suggest that high doses of SAK-RGD-K2-Hirul bear the risk of bleeding.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
SAK-RGD-K2-Hir and SAK-RGD-K2-Hirul are recombinant proteins that are derivatives of r-SAK (recombinant staphylokinase).
Warum dies für die Hirudotherapie relevant ist
Diese Studie untersuchte das thrombolytische Potenzial eines rekombinanten Staphylokinase-Derivats, SAK-RGD-K2-Hirul, das ein antithrombotisches Hirulog-Fragment (abgeleitet von Hirudin) enthält, in einem elektrisch induzierten Karotisarterienthrombose-Modell bei Ratten. Eine Bolusinjektion von SAK-RGD-K2-Hirul verbesserte die Karotis-Durchgängigkeit und reduzierte das Thrombusgewicht wirksamer als r-SAK allein und war vergleichbar mit dem hirudinhaltigen SAK-RGD-K2-Hir, jedoch war die Gabe hoher Dosen mit einem Blutungsrisiko verbunden. Dies belegt den funktionellen Beitrag eines von Hirudin abgeleiteten Peptids innerhalb eines multimodalen thrombolytischen Fusionsproteins und ist relevant für das Design hirudinbasierter antithrombotischer Arzneimittel. Einschränkung: Es handelt sich um eine tierexperimentelle Studie (Ratte) zu einem rekombinanten Fusionsprotein, nicht um natürliches Hirudin oder lebende Blutegeltherapie, und es wurde kein Vorteil gegenüber der hirudinfragmenthaltigen Variante gezeigt.
Zitation
New derivative of staphylokinase SAK-RGD-K2-Hirul exerts thrombolytic effects in the arterial thrombosis model in rats
Szemraj J et al. · Pharmacological reports : PR, 2011
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