A novel insight into the mechanism of the antithrombotic action of defibrotide

Tettamanti, R; Bianchi, Giorgio; Vitte, Pierre-Alain; Kato, G.; Porta, Roberto; Thiemermann, Christoph; Pescador, Rodolfo; Mantovani, M

doi:10.1016/0024-3205(92)90565-7

Cited by 10 publications

(9 citation statements)

References 18 publications

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“…DFT has antithrombotic-thrombolytic activity in several different experimental models (28,29,30,34,41,53,57,62,64,78). DFT increases thrombomodulin (TM) (82), protein C (4), t-PA (42,44,45), Tissue Factor Pathway Inhibitor (TFPI) (52), PGI 2 (8,9,35,48), PGI 2 receptors on the surface of platelets and their affinity for PGI 2 (49), production of NO (50) and NOS activity, and NOS protein (36).…”

Section: Change In Phenotype From Antithrombotic To Prothromboticmentioning

confidence: 99%

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Defibrotide and Endothelial Cell Activation

Pescador¹,

Porta²,

Ferro³

2000

Cardiovascular Drug Reviews

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Defibrotide has several activities [profibrinolytic, antithrombotic-thrombolytic, antiischemic (heart, liver, kidney, skin, brain), antishock, antiatherosclerotic, and antirejection]. This host of activities has puzzled several people accustomed to the concept: one drug -one activity. But, if you see defibrotide as an antiendothelial cell activation drug, each piece of the puzzle will neatly fit into its right place and the host of activities becomes an array of activities. In fact the polyhedric inflammatory process is the common background of seemingly different illnesses, both acute and chronic. So the old concept of one drug-one activity proves true; one drug: defibrotide -one activity; antiendothelial cell activation activity.

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Section: Change In Phenotype From Antithrombotic To Prothromboticmentioning

confidence: 99%

“…DFT decreases PAF (8), PAI (42,44), TF (32) and TXA 2 (11). DFT deactivates platelets (11), monocyte/macrophages (18,78), and PMNs (12,37,75). Leukocytosis and thrombocytosis are decreased by DFT (60).…”

Section: Change In Phenotype From Antithrombotic To Prothromboticmentioning

confidence: 99%

Defibrotide and Endothelial Cell Activation

Pescador¹,

Porta²,

Ferro³

2000

Cardiovascular Drug Reviews

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“…16,17 Besides, DFT has different activities [pro-fibrinolytic, anti-thrombotic, thrombolytic, anti-ischemic, anti-shock and anti-atherosclerotic] that fit antiendothelial cell activation activity. 14,[18][19][20] Thus, our present study was designed to investigate the additive effect of human bone marrow-derived (hBM) MSC and DFT in an experimental rat model of arterial thrombosis. We hypothesized that this protocol would increase the frequency of circulating endothelial precursors and promote the formation of new blood vessels (neovascularization), thereby enhancing the resolution of thrombi, and building a novel treatment regimen for arterial thrombosis.…”

Section: Introductionmentioning

confidence: 99%

Additive effect of mesenchymal stem cells and defibrotide in an arterial rat thrombosis model

et al. 2017

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Background/aim. In this study, we aimed to investigate the additive effect of mesenchymal stem cells (MSC) and defibrotide (DFT) in a rat model of femoral arterial thrombosis. Methods. Thirty Sprague Dawley rats were included. An arterial thrombosis model by ferric chloride (FeCl3) was developed in the left femoral artery. The rats were equally assigned to 5 groups: Group 1-Sham-operated (without arterial injury); Group 2-Phosphate buffered saline (PBS) injected; Group 3-MSC; Group 4-DFT; Group 5-MSC + DFT. All had two intraperitoneal injections of 0.5 ml: the 1 st injection was 4 h after the procedure and the 2 nd one 48 h after the 1 st injection. The rats were sacrificed 7 days after the 2 nd injection. Results. Although the use of human bone marrow-derived (hBM) hBM-MSC or DFT alone enabled partial resolution of the thrombus, combining them resulted in near-complete resolution. Neovascularization was two-fold better in hBM-MSC + DFT treated rats (11.6 ± 2.4 channels) compared with the hBM-MSC (3.8 ± 2.7 channels) and DFT groups (5.5 ± 1.8 channels) (P < 0.0001 and P= 0.002, respectively). Conclusion. The combined use of hBM-MSC and DFT in a rat model of arterial thrombosis showed additive effect resulting in near-complete resolution of the thrombus.

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“…16,17 Asimismo, el DFT posee diferentes propiedades (profibrinolíticas, antitrombóticas, trombolíticas, antiisquémicas, antichoque y antiateroscleróticas) que se complementan con la actividad relacionada con la activación de anticuerpos anticélulas endoteliales. 14,[18][19][20] Por lo tanto, el presente estudio se diseñó para investigar el efecto aditivo de las MSC derivadas de médula ósea humana (hBM) y el DFT en un modelo experimental de trombosis arterial en ratas. Planteamos como hipótesis que este protocolo aumentaría la frecuencia de los precursores endoteliales circulantes y estimularía la formación de vasos sanguíneos nuevos (neovascularización).…”

Section: Introductionunclassified