title: Type I phosphoinositide 3-kinases: potential antithrombotic targets?
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.
authors.affiliation: Australian Centre for Blood Diseases, Monash University, 6th Level Burnet Building, Alfred Medical Research and Education Precinct (AMREP), 89 Commercial Road, Melbourne, Victoria, 3004, Australia. Shaun.Jackson@med.monash.edu.au
authors.forename: S F
authors.initials: SF
authors.lastname: Jackson
authors.forename: S M
authors.initials: SM
authors.lastname: Schoenwaelder
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D020033:Protein Isoforms / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control / Q000628:therapy*
chemical_list: D020033:Protein Isoforms; D019869:Phosphatidylinositol 3-Kinases