Abstract
Arterial thrombosis is the single most common cause of death and disability in industrialized societies and is the primary pathogenic mechanism underlying acute myocardial infarction and ischemic stroke. Platelets play a central role in this process, and as a consequence, a great deal of effort has gone into identifying the mechanisms regulating the adhesive function of platelets. Platelet adhesion is controlled by intracellular signaling pathways, with growing evidence for a major role for phosphoinositide 3-kinases (PI3Ks) in this process. Platelets express all type I PI3K isoforms, including p110alpha, p110beta, p110delta and p110gamma, with recent evidence suggesting important roles for p110gamma and p110beta in regulating distinct phases of the platelet activation process. Deficiency of p110 gamma or inhibition of p110beta produces a marked defect in arterial thrombosis without a corresponding increase in bleeding time, raising the possibility that inhibition of one or more PI3K isoforms may represent an effective antithrombotic approach.
Citations
Nov 9, 2010·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·David Stegner, Bernhard Nieswandt
Sep 11, 2007·Blood·Ingeborg Hers
May 12, 2009·Blood·Dharmendra PandeyWolfgang Siess
Sep 30, 2009·Blood·Jennifer L CostantiniAaron J Marshall
Jan 12, 2012·Blood·Kristina GegenbauerAlbert Smolenski
Jun 16, 2012·PloS One·Stefanie KrajewskiAndreas Straub
Nov 7, 2012·The Journal of Chemical Physics·Hans Behringer, Ralf Eichhorn
May 3, 2011·The Journal of Chemical Physics·Peter Hugo Nelson
Jan 2, 2014·Analytical Biochemistry·Mahesh YanamandraSayan Mitra
Dec 31, 2014·Expert Opinion on Drug Discovery·Mahesh YanamandraArchana Giri
Feb 16, 2013·Trends in Pharmacological Sciences·Hashem A Dbouk, Jonathan M Backer
Nov 30, 2010·Advances in Enzyme Regulation·Jasna MarjanovicPhilip W Majerus
Aug 19, 2009·Fitoterapia·Leyre Navarro-NúñezJosé Rivera
Feb 22, 2013·Thrombosis and Haemostasis·Wen-Ying ChuangChin-Chung Wu
Nov 17, 2009·Immunological Reviews·Ting-Ting ZhangAaron J Marshall
Jun 4, 2015·Journal of Thrombosis and Haemostasis : JTH·T A BlairI Hers
Aug 5, 2015·Advances in Biological Regulation·Adrien LupieriMuriel Laffargue
Jun 13, 2013·Blood·Sang H Min, Charles S Abrams
Dec 13, 2006·Circulation Research·Stefan Offermanns
Jun 7, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Thomas A BlairIngeborg Hers
Jul 15, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dong LiuJude E Uzonna
Jan 7, 2020·Current Topics in Medicinal Chemistry·Rammohan R Y Bheemanaboina
Oct 17, 2017·Journal of Immunoassay & Immunochemistry·Mahesh YanamandraSayan Mitra
Mar 19, 2021·Science Advances·Chang LiuQiang Qiu