G13-mediated signaling as a potential target for antiplatelet drugs

Abstract

The activation of platelets at sites of vascular injury is essential for primary hemostasis, but also underlies arterial thrombosis leading to myocardial infarction or stroke. The inhibition of platelet function is therefore a major strategy to prevent and treat arterial thrombosis. Platelet stimuli like ADP, thrombin or thromboxane A(2) activate receptors that are coupled to heterotrimeric G proteins to regulate intracellular signaling pathways. Activation of platelets through these receptors has been shown to involve signaling through various heterotrimeric G proteins. The G protein G(13), which is able to link receptors to the Rho/Rho-kinase pathway, has recently been shown to be critically involved in platelet activation and to play an important role in platelet-dependent arterial thrombosis. The G(13)-mediated signaling pathway may therefore be an interesting new target for antiplatelet drugs.