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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1293.)
© 2005 American Heart Association, Inc.

Thrombosis

Importance of Platelet Phospholipase C2 Signaling in Arterial Thrombosis as a Function of Lesion Severity

Christelle Nonne; Nadège Lenain; Béatrice Hechler; Pierre Mangin; Jean-Pierre Cazenave; Christian Gachet; François Lanza

From INSERM U.311, Etablissement Français du Sang-Alsace, Strasbourg, France.

Correspondence François Lanza or Christian Gachet, INSERM U.311, Etablissement Français du Sang-Alsace, 10 rue Spielmann, BP 36, 67065 Strasbourg Cedex, France. E-mail francois.lanza{at}efs-alsace.fr or christian.gachet@efs-alsace.fr

Objective— Platelet activation occurs in response to adhesion receptors for von Willebrand factor (GPIb-V-IX) and collagen (GPVI and ₂ß₁ integrin) acting upstream of phospholipase C (PLC) 2. However, PLCß transduces signals from Gq 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, PLC2 knockout mice were studied in blood perfusion assays over fibrillar collagen and in a laser-induced mesenteric artery model of thrombosis. In vitro, PLC2-deficient platelets formed a single layer incapable of generating a thrombus on collagen, whereas Gq-deficient platelets formed reduced size aggregates compared with wild-type cells. In the in vivo model, PLC2^–/– 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 Gq^–/– mice in both levels of injury.

Conclusions— These results demonstrate that signaling through PLC2 plays an important role in arterial thrombosis, but that its contribution depends on the severity of the vascular lesion.

This study evaluated the role of adhesion receptors signaling through PLC2 in arterial thrombosis. PLC2-deficient mice showed resistance to thrombus formation in superficial lesions but productive thrombosis after a more severe laser injury formation. In contrast, resistance to thrombosis was observed in Gq^–/– mice in both levels of injury.

Key Words: adhesion • mouse model • phospholipase C • platelet thrombosis

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