Endothelial P2X7 promotes venous thromboembolism - 17/02/23

Doi : 10.1016/j.rmr.2022.11.042 
E.L. Ollivier 1, , V. Gourdou-Latyszenok 1, F. Couturaud 2, C. Lemarie 1
1 UMR 1304, GETBO, Inserm, UFR médecine, UBO, Brest, France 
2 UMR 1304, GETBO, Inserm, CHRU Brest, département de médecine interne et pneumologie UFR médecine, UBO, Brest, France 

Corresponding author.



Venous thromboembolism (VTE) affects 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 thrombus formation and therefore in VTE mechanisms. In pathological conditions, adenosine triphosphate (ATP) is released in the extracellular compartment and is recognized as a danger signal by several cell types including endothelial cells. Recent data indicated that the CD39/CD73 system involved in the metabolism of ATP into AMP might protects 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.


To determine how the endothelial P2X7 receptor contributes to venous thromboembolism.


HUVECs were incubated with BzATP, thrombin or both. HUVECs were primed with TNF-alpha prior 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.


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 appears to be associated with an increased expression of IL-1b and downregulation of thrombomodulin expression. The expression of adhesion molecules, ICAM-1 and VCAM-1, tends to increase.


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

El texto completo de este artículo está disponible en PDF.


© 2022  Publicado por Elsevier Masson SAS.

    Exportación citas

  • Fichero

  • Contenido

Vol 40 - N° 2

P. 129-130 - février 2023 Regresar al número
Artículo precedente Artículo precedente
  • Short-term mechanisms activated by NGF to induce pulmonary arterial hyperreactivity
  • C. Bouchet, G. Cardouart, M. Douard, Z. Kmecova, P. Robillard, F. Delcambre, R. Marthan, P. Berger, C. Guibert, V. Freund-Michel
| Artículo siguiente Artículo siguiente
  • Implication du stress oxydant et de la signalisation calcique dans les altérations induites par des nanoparticules d’oxyde de nickel dans des cellules endothéliales d’artère pulmonaire humaine
  • O. Germande, J. Deweirdt, C. Guibert, M. Baudrimont, I. Baudrimont

¿Ya suscrito a @@106933@@ revista ?