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Endothelial P2X7 promotes venous thromboembolism - 09/03/22

Doi : 10.1016/j.rmr.2022.02.024 
E. Olliver , V. Gourdou-Latyszenok, F. Couturaud, C. Lemarie
 UFR Medecine, EA3878, GETBO, Brest, France 

Corresponding author.

Résumé

Background

Venous thromboembolism (VTE) afflicts 117 people per 100,000 each year and is an important cause of morbidity and mortality. VTE can lead to 1) death through pulmonary embolism, 2) the post-thrombotic syndrome, or 3) chronic pulmonary hypertension resulting in significant chronic respiratory compromise. Inflammatory pathways are intricately involved in venous thromboembolism mechanisms. In pathological conditions, adenosine triphosphate (ATP) is released in the extracellular compartment and is recognized as a danger signal. Recent data indicated that the CD39/CD73 system involved in the metabolism of ATP into AMP might protect against thrombosis by downregulating the pro-inflammatory pathway of the inflammasome. ATP can also interact with the P2X7 receptor involved in inflammation causing a wide range of responses. Determining how the endothelial P2X7 receptor contribute to venous thromboembolism.

Methods

HUVEC were incubated with BzATP, thrombin or both. In some experiment, HUVEC were primed with TNFaprior to stimulation. We used immunofluorescence, western blot and real-time quantitative PCR analyses to assess P2X7 expression by endothelial cells, activation of p38 and NFkB activation and expression of pro-inflammatory and pro- coagulant genes.

Results

We confirmed that endothelial cells expressed P2X7 in vitro in HUVECs and in vivo after induction of venous thrombosis by ligation of the inferior vena cava. Treatment of endothelial cells with BzATP and thrombin induced the activation of p38 and NFkB signaling pathways. This was associated with an increased expression of IL-1b and tissue factor and downregulation of thrombomodulin expression.

Summary/Conclusion

Our data suggest that ATP released in the extracellular space following cell damage or activation induced the inflammasome in endothelial through P2X7 activation. P2X7 might have a pro-thrombotic role exacerbating venous thromboembolism.

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Keyword : Circulation


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© 2022  Publié par Elsevier Masson SAS.
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Vol 39 - N° 2

P. 118 - février 2022 Retour au numéro
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