Novel Integrin-Specific Targets for Anti-Platelet Therapies

Abstract

Extensive study in integrin research has seen the platelet specific receptor alpha(IIb)beta(3) (Glycoprotein GPIIb/IIIa) under much scrutiny, and provided vast information as to the workings of this integrin within the blood. Glanzmann's thrombasthenia, a rare autosomal recessive bleeding disorder, highlights the vital role played by this receptor in platelet function. Glanzmann's thrombasthenic platelets fail to aggregate due to a lack of surface expression of functional alpha(IIb) or beta(3) on the platelet surface. However, little is known about the precise molecular mechanisms involved in the operation of this receptor on the platelet surface. Clinical trials using intravenous antagonists to this receptor have shown them to be effective anti-thrombotics. However the recent observations that the oral alpha(IIb)beta(3)antagonists have failed to show benefits in the treatment of acute coronary syndromes, and in fact, increase mortality, underscores the necessity for a more complete understanding of alpha(IIb)beta(3) and its functions. A more profound knowledge of the precise nature of the platelet integrin-activation, along with an understanding of its interactions with cellular signaling proteins, will undoubtedly lead to the identification of novel strategies for the effective inhibition of platelet integrin function.