| First Author | Hirsch E | Year | 2001 |
| Journal | FASEB J | Volume | 15 |
| Issue | 11 | Pages | 2019-21 |
| PubMed ID | 11511514 | Mgi Jnum | J:120151 |
| Mgi Id | MGI:3703955 | Doi | 10.1096/fj.00-0810fje |
| Citation | Hirsch E, et al. (2001) Resistance to thromboembolism in PI3Kgamma-deficient mice. FASEB J 15(11):2019-21 |
| abstractText | 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. |
