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Defibrotide reduces procoagulant activity and increases fibrinolytic properties of endothelial cells

Leukemia volume 17, pages 1636–1642 (2003)Cite this article

Abstract

Defibrotide (DF), a polydeoxyribonucleotide with antithrombotic properties, has recently proven effective in patients with severe hepatic veno-occlusive disease (VOD), a life-threatening complication of high-dose chemo/radiotherapy regimens for stem cell transplantation. To understand the mechanism of its beneficial effect, we studied the impact of DF on the expression of tissue factor (TF) and fibrinolytic proteins (PAI-1 and t-PA) on endothelial cells. The in vitro response to DF of two types of human endothelial cells (ECs) of different origins, that is from macrovascular (HUVEC) and microvascular (HMEC-1 cell line) beds, was evaluated in the presence or absence of a proinflammatory stimulus (ie bacterial endotoxin, LPS). The results show that DF was able to significantly reduce the LPS-induced TF expression by HMEC-1, and less prominently by HUVEC. In addition, DF importantly influenced the fibrinolytic properties of both HMEC-1 and HUVEC. Specifically, it dose-dependently counteracted the LPS-induced increase in PAI-1 levels and decrease in t-PA activity expression. It also significantly incremented t-PA antigen in resting EC. Decreasing the procoagulant activity and increasing the fibrinolytic potential of EC favors an anticoagulant phenotype of the endothelium, which may protect from fibrin deposition and vascular occlusion.

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Acknowledgements

We acknowledge Dr M Iacobelli for providing Defibrotide (Gentium SpA, Villa Guardia, Como Italy) for helpful discussion and for providing DF. This work was partially supported by a grant to AF from the ‘Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.)’.

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  1. Department of Hematology, Ospedali Riuniti, Bergamo, Italy

    A Falanga, A Vignoli, M Marchetti & T Barbui

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  1. A Falanga
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  4. T Barbui
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Falanga, A., Vignoli, A., Marchetti, M. et al. Defibrotide reduces procoagulant activity and increases fibrinolytic properties of endothelial cells. Leukemia 17, 1636–1642 (2003). https://doi.org/10.1038/sj.leu.2403004

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