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Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1293-8. Epub 2005 Mar 17.

Importance of platelet phospholipase Cgamma2 signaling in arterial thrombosis as a function of lesion severity.

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  • 1INSERM U.311, Etablissement Fran├žais du Sang-Alsace, Strasbourg, France.

Abstract

OBJECTIVE:

Platelet activation occurs in response to adhesion receptors for von Willebrand factor (GPIb-V-IX) and collagen (GPVI and alpha2beta1 integrin) acting upstream of phospholipase C (PLC) gamma2. However, PLCbeta transduces signals from Galphaq protein-coupled receptors for soluble agonists (P2y1, TxA2/TP, and thrombin/PAR). A Gi-dependent pathway amplifies most of these responses.

METHODS AND RESULTS:

To evaluate the role of adhesion receptors signaling in arterial thrombosis, PLCgamma2 knockout mice were studied in blood perfusion assays over fibrillar collagen and in a laser-induced mesenteric artery model of thrombosis. In vitro, PLCgamma2-deficient platelets formed a single layer incapable of generating a thrombus on collagen, whereas Galphaq-deficient platelets formed reduced size aggregates compared with wild-type cells. In the in vivo model, PLCgamma2-/- mice displayed defective thrombus formation in superficial lesions but productive thrombosis after a more severe laser injury. In contrast, resistance to thrombosis was observed in Galphaq-/- mice in both levels of injury.

CONCLUSIONS:

These results demonstrate that signaling through PLCgamma2 plays an important role in arterial thrombosis, but that its contribution depends on the severity of the vascular lesion.

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