Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.

Haematologica
Yona NadirIsrael Vlodavsky

Abstract

Heparanase is an endo-β-D-glucuronidase dominantly involved in tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is involved in the regulation of the hemostatic system. Our hypothesis was that heparanase is directly involved in activation of the coagulation cascade. Activated factor X and thrombin were studied using chromogenic assays, immunoblotting and thromboelastography. Heparanase levels were measured by enzyme-linked immunosorbent assay. A potential direct interaction between tissue factor and heparanase was studied by co-immunoprecipitation and far-western assays. Interestingly, addition of heparanase to tissue factor and activated factor VII resulted in a 3- to 4-fold increase in activation of the coagulation cascade as shown by increased activated factor X and thrombin production. Culture medium of human embryonic kidney 293 cells over-expressing heparanase and its derivatives increased activated factor X levels in a non-enzymatic manner. When heparanase was added to pooled normal plasma, a 7- to 8-fold increase in activated factor X level was observed. Subsequently, we searched for clinical data supporting this newly identified role of heparanase. Plasma samples from 35 patients with acute l...Continue Reading

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Citations

Nov 20, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Miry BlichIsrael Vlodavsky
Oct 23, 2015·Thrombosis and Haemostasis·Inna KoganY Nadir
Jul 18, 2014·Thrombosis and Haemostasis·E AxelmanY Nadir
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Jun 17, 2021·Bioscience Reports·Safa KinanehShadi Hamoud

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