References of "Kuijpers, Marijke"
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See detailDUSP3 Phosphatase Deficiency or Inhibition Limit Platelet Activation and Arterial Thrombosis
Musumeci, Lucia ULg; Kuijpers, Marijke; Gilio, Karen et al

in Circulation (in press)

Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet ... [more ▼]

Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet activation is of importance for the development of improved therapies. Recently, protein tyrosine phosphatases (PTPs) have emerged as critical regulators of platelet function. Methods and Results This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated through the collagen receptor glycoprotein VI (GPVI) and the C-type lectin-like receptor 2 (CLEC-2). DUSP3-deficient mice were more resistant to collagen- and epinephrine-induced thromboembolism, compared to wild-type mice, and showed severely impaired thrombus formation upon ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of PLCγ2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was developed. This compound specifically inhibited collagen and CLEC-2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells. Conclusions DUSP3 plays a selective and essential role in collagen- and CLEC-2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic for arterial thrombosis. This is the first time a PTP, implicated in platelet signaling, has been targeted with a small-molecule drug. [less ▲]

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See detailFacilitating roles of murine platelet glycoprotein Ib and alphaIIbbeta3 in phosphatidylserine exposure during vWF-collagen-induced thrombus formation.
Kuijpers, Marijke; Schulte, V.; Oury, Cécile ULg et al

in Journal of Physiology (2004)

This work indicates that, under physiological conditions of flow, both adhesive receptors GPIb and alphaIIbbeta3 facilitate GPVI-mediated PS exposure by stabilizing platelet binding to collagen. Hence ... [more ▼]

This work indicates that, under physiological conditions of flow, both adhesive receptors GPIb and alphaIIbbeta3 facilitate GPVI-mediated PS exposure by stabilizing platelet binding to collagen. Hence, these glycoproteins have an assistant procoagulant role in collagen-dependent thrombus formation, which is most prominent at reduced GPVI activity and is independent of the presence of thrombin. [less ▲]

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See detailOverexpression of the platelet P2X1 ion channel in transgenic mice generates a novel prothrombotic phenotype.
Oury, Cécile ULg; Kuijpers, Marijke; Toth-Zsamboki, Emese et al

in Journal of Thrombosis and Haemostasis (2003)

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See detailGlycoprotein Ib and integrin alphaIIbbeta3 contribute to GPVI-dependent vWF-collagen induced thrombus formation under flow
Kuijpers, Marijke; Oury, Cécile ULg; Schulte, V. et al

in Journal of Thrombosis and Haemostasis [=JTH] (2003)

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See detailOverexpression of the platelet P2X1 ion channel in transgenic mice generates a novel prothrombotic phenotype.
Oury, Cécile ULg; Kuijpers, Marijke; Toth-Zsamboki, Emese et al

in Blood (2003)

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 ... [more ▼]

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. [less ▲]

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See detailIncreased platelet reactivity to collagen in transgenic mice overexpressing the P2X1 ion channel.
Oury, Cécile ULg; Kuijpers, marijke; Toth-Zsamboki, Emese et al

in Haematologica (2002), 87

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See detailEnhanced Platelet Reactivity to Collagen and Shear Stress in Transgenic Mice Overexpressing the Platelet P2X1 Ion Channel
Oury, Cécile ULg; Kuijpers, Marijke; Toth-Zsamboki, Emese et al

in Blood (2002), 100

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