Regulator of G Protein Signaling 6 Negatively Regulates Platelet Activation and Arterial Thrombosis in Mice

Background: Platelet activation via G protein-coupled receptors (GPCRs) is central to arterial thrombosis. P2Y12 is a canonical Gi-coupled receptor mediating ADP-dependent platelet activation, yet the role of Regulator of G protein Signaling 6 (RGS6), a modulator of Gi signaling, in platelet function and thrombosis remains unclear. Objectives: /Gi signaling. Methods: /Gi signaling was further evaluated using a cAMP-responsive luciferase reporter assay in HEK293 cells. Results: with clopidogrel abolished the genotype-dependent difference in thrombosis in vivo. Conclusions: /Gi signaling and thrombus formation. Loss of RGS6 enhances ADP-dependent platelet activation and accelerates arterial thrombosis, establishing RGS6 as an endogenous brake on platelet activation.