A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo..pdf (245.96 kB)

A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo

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journal contribution
posted on 24.05.2016 by Béatrice Hechler, Nadège Lenain, Patrizia Marchese, Catherine Vial, Véronique Heim, Monique Freund, Jean-Pierre Cazenave, Marco Cattaneo, Zaverio M. Ruggeri, Richard Evans, Christian Gachet
The P2X₁ receptor is a fast ATP-gated cation channel expressed in blood platelets, where its role has been difficult to assess due to its rapid desensitization and the lack of pharmacological tools. In this paper, we have used P2X₁⁻/⁻ and wild-type mouse platelets, treated with apyrase to prevent desensitization, to demonstrate the function of P2X₁ in the response to thrombogenic stimuli. In vitro, the collagen-induced aggregation and secretion of P2X₁-deficient platelets was decreased, as was adhesion and thrombus growth on a collagen-coated surface, particularly when the wall shear rate was elevated. In vivo, the functional role of P2X₁ could be demonstrated using two models of platelet-dependent thrombotic occlusion of small arteries, in which blood flow is characterized by a high shear rate. The mortality of P2X₁⁻/⁻ mice in a model of systemic thromboembolism was reduced and the size of mural thrombi formed after a laser-induced vessel wall injury was decreased as compared with normal mice, whereas the time for complete thrombus removal was shortened. Overall, the P2X₁ receptor appears to contribute to the formation of platelet thrombi, particularly in arteries in which shear forces are high.

History

Citation

Journal of Experimental Medicine, 2003, 198 (4), pp. 661-667

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Molecular & Cell Biology

Version

VoR (Version of Record)

Published in

Journal of Experimental Medicine

Publisher

Rockefeller University Press

issn

0022-1007

eissn

1540-9538

Acceptance date

12/06/2003

Copyright date

2003

Available date

24/05/2016

Publisher version

http://jem.rupress.org/content/198/4/661

Language

en

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