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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2005-5-5
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pubmed:abstractText |
Platelet activation at sites of vascular injury is essential for the arrest of bleeding; however, excessive platelet accumulation at regions of atherosclerotic plaque rupture can result in the development of arterial thrombi, precipitating diseases such as acute myocardial infarction and ischemic stroke. Rheological disturbances (high shear stress) have an important role in promoting arterial thrombosis by enhancing the adhesive and signaling function of platelet integrin alpha(IIb)beta(3) (GPIIb-IIIa). In this study we have defined a key role for the Type Ia phosphoinositide 3-kinase (PI3K) p110beta isoform in regulating the formation and stability of integrin alpha(IIb)beta(3) adhesion bonds, necessary for shear activation of platelets. Isoform-selective PI3K p110beta inhibitors have been developed which prevent formation of stable integrin alpha(IIb)beta(3) adhesion contacts, leading to defective platelet thrombus formation. In vivo, these inhibitors eliminate occlusive thrombus formation but do not prolong bleeding time. These studies define PI3K p110beta as an important new target for antithrombotic therapy.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1078-8956
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pubmed:author |
pubmed-author:AbbottBelindaB,
pubmed-author:AndersonKaren EKE,
pubmed-author:AngusJames AJA,
pubmed-author:DanieleNathalieN,
pubmed-author:DopheideSacha MSM,
pubmed-author:GiulianoSimonS,
pubmed-author:GoncalvesIsaacI,
pubmed-author:HughanSascha CSC,
pubmed-author:JacksonShaun PSP,
pubmed-author:JonesCatherineC,
pubmed-author:KencheVijayaV,
pubmed-author:KulkarniSuhasiniS,
pubmed-author:LuLucyL,
pubmed-author:NesbittWarwick SWS,
pubmed-author:PrabaharanHishaniH,
pubmed-author:RobertsonAlan DAD,
pubmed-author:SalemHatem HHH,
pubmed-author:SaylikDilekD,
pubmed-author:SchoenwaelderSimone MSM,
pubmed-author:ShepherdPeter RPR,
pubmed-author:SmithGregg DGD,
pubmed-author:SturgeonSharelle ASA,
pubmed-author:ThompsonPhilip EPE,
pubmed-author:WrightChristine ECE,
pubmed-author:YapCindy LCL,
pubmed-author:YuanYupingY
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pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
507-14
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15834429-Animals,
pubmed-meshheading:15834429-Arteries,
pubmed-meshheading:15834429-Bleeding Time,
pubmed-meshheading:15834429-Blood Platelets,
pubmed-meshheading:15834429-Flow Cytometry,
pubmed-meshheading:15834429-Isoenzymes,
pubmed-meshheading:15834429-Mice,
pubmed-meshheading:15834429-Mice, Knockout,
pubmed-meshheading:15834429-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15834429-Platelet Adhesiveness,
pubmed-meshheading:15834429-Platelet Glycoprotein GPIIb-IIIa Complex,
pubmed-meshheading:15834429-Rheology,
pubmed-meshheading:15834429-Serotonin,
pubmed-meshheading:15834429-Signal Transduction,
pubmed-meshheading:15834429-Thrombosis,
pubmed-meshheading:15834429-rap GTP-Binding Proteins
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pubmed:year |
2005
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pubmed:articleTitle |
PI 3-kinase p110beta: a new target for antithrombotic therapy.
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pubmed:affiliation |
Australian Centre for Blood Diseases, Monash University, 6th Floor Burnet Building Alfred Medical Research and Education Precinct, Prahran, Victoria, Australia 3181. shaun.jackson@med.monash.edu.au
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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