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PI 3-kinase p110beta: a new target for antithrombotic therapy.
Jackson, Shaun P; Schoenwaelder, Simone M; Goncalves, Isaac; Nesbitt, Warwick S; Yap, Cindy L; Wright, Christine E; Kenche, Vijaya; Anderson, Karen E; Dopheide, Sacha M; Yuan, Yuping; Sturgeon, Sharelle A; Prabaharan, Hishani; Thompson, Philip E; Smith, Gregg D; Shepherd, Peter R; Daniele, Nathalie; Kulkarni, Suhasini; Abbott, Belinda; Saylik, Dilek; Jones, Catherine; Lu, Lucy; Giuliano, Simon; Hughan, Sascha C; Angus, James A; Robertson, Alan D; Salem, Hatem H.
Afiliación
  • Jackson SP; 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
Nat Med ; 11(5): 507-14, 2005 May.
Article en En | MEDLINE | ID: mdl-15834429
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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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arterias / Trombosis / Transducción de Señal / Adhesividad Plaquetaria / Complejo GPIIb-IIIa de Glicoproteína Plaquetaria / Fosfatidilinositol 3-Quinasas Límite: Animals Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2005 Tipo del documento: Article Pais de publicación: Estados Unidos
Buscar en Google
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arterias / Trombosis / Transducción de Señal / Adhesividad Plaquetaria / Complejo GPIIb-IIIa de Glicoproteína Plaquetaria / Fosfatidilinositol 3-Quinasas Límite: Animals Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2005 Tipo del documento: Article Pais de publicación: Estados Unidos