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A role of the fast ATP-gated P2X(1) cation channel in thrombosis of small arteries in vivo

Academic Article
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Overview

authors

  • Hechler, B.
  • Lenain, N.
  • Marchese, P.
  • Vial, C.
  • Heim, W.
  • Freund, M.
  • Cazenave, J. P.
  • Cattaneo, M.
  • Ruggeri, Zaverio
  • Evans, R.
  • Gachet, C.

publication date

  • August 2003

journal

  • Journal of Experimental Medicine  Journal

abstract

  • 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.

subject areas

  • Adenosine Triphosphate
  • Animals
  • Apyrase
  • Arteries
  • Blood Platelets
  • Calcium
  • Collagen
  • Lung
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Platelet Aggregation
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X
  • Shear Strength
  • Thrombosis
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Research

keywords

  • P2 receptors
  • arterial thrombosis
  • knockout mice
  • platelet
  • shear forces
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Identity

PubMed Central ID

  • PMC2194166

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.20030144

PubMed ID

  • 12913094
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Additional Document Info

start page

  • 661

end page

  • 667

volume

  • 198

issue

  • 4

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