on March 13, 2003
Published online before print March 13, 2003, doi: 10.1161/01.ATV.0000066686.46338.F1
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Submitted on January 16, 2003
Accepted on February 24, 2003
Integrin 
IIb
3 and Its Antagonism
Martin J. Quinn ;
From the Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Departments of Molecular Cardiology and Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio.
* To whom correspondence should be addressed. E-mail: plowe{at}ccf.org.
Abstract--
IIb
3, the major membrane protein on the surface of platelets, is a member of the integrin family of heterodimeric adhesion receptors. The IIb and 3 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 IIb3 into a functional receptor for fibrinogen or von Willebrand factor to support platelet aggregation and thrombus formation. These functions of IIb3 have been targeted for antithrombotic therapy, and intravenous IIb3 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 IIb3 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 IIb3 and platelets in the context of the new structural insights may explain its salutary and potential deleterious effects.
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