Article (Scientific journals)
Overexpression of the platelet P2X1 ion channel in transgenic mice generates a novel prothrombotic phenotype.
Oury, Cécile; Kuijpers, Marijke; Toth-Zsamboki, Emese et al.
2003In Blood
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Keywords :
thrombosis; purinergic receptors; transgenic mice
Abstract :
[en] This study describes transgenic mice overexpressing the human P2X(1) ion channel in the megakaryocytic cell lineage. Platelets from these mice display increased secretion and aggregation evoked by low doses of collagen, convulxin, or the thromboxane A(2) mimetic U46619. Perfusing whole blood from transgenic mice over collagen fibers at a shear rate of 1000 seconds(-1) resulted in increased P2X(1)-dependent aggregate formation and phosphatidylserine exposure. Platelet hyperreactivity to collagen was correlated with up-regulated extracellular signal-regulated kinase 2 (ERK2) phosphorylation. In a viscometer, shear stress caused potent aggregation of transgenic platelets under conditions in which wild-type platelets did not aggregate. In an in vivo model of thromboembolism consisting of intravenous injection of a low dose of collagen plus epinephrine, transgenic mice died more readily than wild-type mice. Preinjection of U0126 not only fully protected transgenic mice against thrombosis, it also enhanced the survival of wild-type mice injected with a higher collagen dose. Hence, the platelet P2X(1) ion channel plays a role in hemostasis and thrombosis through its participation in collagen-, thromboxane A(2)-, and shear stress-triggered platelet responses. Activation of the ERK2 pathway is instrumental in these processes.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Oury, Cécile  ;  Katholieke Universiteit Leuven - KUL > Molecular and Cellular Medicine > CMVB
Kuijpers, Marijke;  Universiteit Maastricht > Biochemistry > CARIM
Toth-Zsamboki, Emese;  Katholieke Universiteit Leuven - KUL > Molecular and Cellular Medicine > CMVB
Bonnefoy, Arnaud;  Katholieke Universiteit Leuven - KUL > Molecular and Cellular Medicine > CMVB
Danloy, Sophie;  Katholieke Universiteit Leuven - KUL > Molecular and Cellular Medicine > CMVB
Vreys, I.;  Katholieke Universiteit Leuven - KUL > Molecular and Cellular Medicine > CMVB
Feijge, Marion;  Universiteit Maastricht > Biochemistry > CARIM
De Vos, Rita;  Katholieke Universiteit Leuven - KUL > Molecular and Cellular Medicine > Morphology and Molecular Pathology
Vermylen, Jos;  Katholieke Universiteit Leuven - KUL > Molecular and Cellular Medicine > CMVB
Hoylaerts, Marc F;  Katholieke Universiteit Leuven - KUL > Molecular and Cellular Medicine > CMVB
Language :
English
Title :
Overexpression of the platelet P2X1 ion channel in transgenic mice generates a novel prothrombotic phenotype.
Publication date :
2003
Journal title :
Blood
ISSN :
0006-4971
eISSN :
1528-0020
Publisher :
American Society of Hematology, Washington, United States - District of Columbia
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 23 September 2009

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