Platelet Integrin αIIbβ3: Mechanisms of Activation and Clustering; Involvement into the Formation of the Thrombus Heterogeneous Structure

Abstract

Abstract— Glycoproteins IIb-IIIa (GPIIb-IIIa), also known as αIIbβ3 integrins, are key platelet adhesion receptors. These molecules are the most abundant (over 10 000 copies per cell) transmembrane receptors playing a crucial role in thrombus formation by promoting platelet aggregation. Integrins need to undergo activation and transit to high-affinity state for their ligands – fibrinogen, fibrin, and von Willebrand factor (VWF) – in order to form bonds between platelets. Activation of integrins is mediated by a set of various messengers through intracellular signalization. Integrins αIIbβ3, like other integrins, are capable of reverse signal transmission inside the cell, called “outside-in” signaling. Recent studies have shown heterogeneity of the thrombus structure and the existence of a stable and dense inner core and a fluid-like loose shell. Since platelet aggregation is provided by integrin-mediated interactions, one can suggest that it is the features of integrin activation and clustering that strongly influence the formation of thrombus architecture. This work is intent on systematizing recent data concerning activation and functioning of platelet integrins αIIbβ3 and searching for correlations between thrombus heterogeneity and the state of integrins on the platelets surface.