Resistance to thromboembolism in PI3Kγ‐deficient mice

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Abstract
SPECIFIC AIMSPI3Kγ has been suggested as a key downstream effector of G-protein-coupled receptors (GPCR) but its specific role in thrombocyte function is still obscure. We investigated the role of PI3Kγ in platelet activation using mice where PI3Kγ expression was genetically ablated. We analyzed platelet aggregation after stimulation with GPCR agonists like ADP and thrombin. We evaluated PKB and fibrinogen receptor activation. Finally, to assess the in vivo consequences of the absence of PI3Kγ in platelets, we analyzed bleeding time and challenged mice in a model of ADP-dependent thromboembolic vascular occlusion.PRINCIPAL FINDINGS1. PI3Kγ-null platelets show impaired aggregation after stimulation with the GPCR agonist ADPActing via GPCRs, ADP is an important signal in the formation of thrombus and involves activation of phosphoinositide 3-kinases (PI3K). Western blot analysis of murine platelets indicates that they express PI3Kα, β, and γ, but not δ. Platelet aggregation was analyzed in whole blood, plat...
Funding Information
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (3100–50506.97)