A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo.
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.
Hechler
Béatrice
B
Institut National de la Santé et de la Recherche Médicale (INSERM) U.311, EFS-Alsace 10, rue Spielmann, BP No. 36, 67065 Strasbourg Cedex, France.
Lenain
Nadege
N
Marchese
Patrizia
P
Vial
Catherine
C
Heim
Véronique
V
Freund
Monique
M
Cazenave
Jean-Pierre
JP
Cattaneo
Marco
M
Ruggeri
Zaverio M
ZM
Evans
Richard
R
Gachet
Christian
C
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D001158:Arteries / Q000166:cytology / Q000473:pathology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D008168:Lung / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010974:Platelet Aggregation / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D033081:Shear Strength; D013927:Thrombosis / Q000378:metabolism* / Q000473:pathology
D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate; D003094:Collagen; D001081:Apyrase; D002118:Calcium