A Role of the Fast ATP-gated P2X1 Cation Channel in Thrombosis of Small Arteries In Vivo

Journal of Experimental Medicine - Tập 198 Số 4 - Trang 661-667 - 2003
Béatrice Hechler1, Nadège Lenain1, Patrizia Marchese2, Catherine Vial3, Véronique Heim1, Monique Freund1, Jean‐Pierre Cazenave1, Marco Cattaneo2,4, Zaverio M. Ruggeri2, Richard J. Evans3, Christian Gachet1
11Institut National de la Santé et de la Recherche Médicale (INSERM) U.311, Etablissement Français du Sang (EFS)-Alsace, 67065 Strasbourg Cedex, France
22The Scripps Research Institute, La Jolla, CA 92037
34Department of Cell Physiology and Pharmacology, University of Leicester, LE1 9HN Leicester, United Kingdom
43Unit of Hematology and Thrombosis, Ospedale San Paolo, Dipartimento di Medicina Chirurgia e Odontoiatria, University of Milan, 20142 Italy

Tóm tắt

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.

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Thông tin xuất bản

Journal of Experimental Medicine

Tập 198 Số 4

661-667

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