Resistance to thromboembolism in PI3Kγ‐deficient mice
- 9 July 2001
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 15 (11), 2019-2021
- https://doi.org/10.1096/fj.00-0810fje
Abstract
Platelet aggregation and subsequent thrombosis are the major cause of ischemic diseases such as heart attack and stroke. ADP, acting via G protein-coupled receptors (GPCRs), is an important signal in thrombus formation and involves activation of phosphoinositide 3-kinases (PI3K). When platelets from mice lacking the G protein-activated PI3Kgamma isoform were stimulated with ADP, aggregation was impaired. Collagen or thrombin, however, evoked a normal response. ADP stimulation of PI3Kgamma-deficient platelets resulted in decreased PKB/Akt phosphorylation and alpha(IIb)beta(3) fibrinogen receptor activation. These effects did not influence bleeding time but protected PI3Kgamma-null mice from death caused by ADP-induced platelet-dependent thromboembolic vascular occlusion. This result demonstrates an unsuspected, well-defined role for PI3Kgamma downstream of ADP and suggests that pharmacological targeting of PI3Kgamma has a potential use as antithrombotic therapy.Keywords
Funding Information
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (3100–50506.97)
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