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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:945.)
© 2003 American Heart Association, Inc.

ATVB In Focus

Integrin _IIbß₃ and Its Antagonism

Martin J. Quinn; Tatiana V. Byzova; Jun Qin; Eric J. Topol; Edward F. Plow

From the Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Departments of Cardiovascular Medicine (M.J.Q., E.J.T.) and Molecular Cardiology (T.V.B., J.Q., E.F.P.), Cleveland Clinic Foundation, Cleveland, Ohio.

Correspondence to Edward F. Plow, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology/NB50, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195. E-mail plowe{at}ccf.org

Series Editor: Lawrence Brass
ATVB In Focus Platelet Activation and the Formation of the Platelet Plug

Previous Brief Reviews in this Series:

•Tsai H-M. Deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura. 2003;23:388–396.

_IIbß₃, the major membrane protein on the surface of platelets, is a member of the integrin family of heterodimeric adhesion receptors. The _IIb and ß₃ subunits are each composed of a short cytoplasmic tail, a single transmembrane domain, and a large, extracellular region that consists of a series of linked domains. Recent structural analyses have provided insights into the organization of this and other integrins and how a signal is initiated at its cytoplasmic tail to transform the extracellular domain of _IIbß₃ into a functional receptor for fibrinogen or von Willebrand factor to support platelet aggregation and thrombus formation. These functions of _IIbß₃ have been targeted for antithrombotic therapy, and intravenous _IIbß₃ antagonists have been remarkably effective in the setting of percutaneous coronary interventions, showing both short-term and long-term mortality benefits. However, the development of oral antagonists has been abandoned on the basis of excess of mortality in clinical trials, and the extension of therapy with existing _IIbß₃ antagonists to broadly treat acute coronary syndromes has not fully met expectations. An in-depth understanding of how antagonists engage and influence the function of _IIbß₃ and platelets in the context of the new structural insights may explain its salutary and potential deleterious effects.

Key Words: platelets • acute coronary syndromes • aggregation • platelet function inhibitors

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