Integrin function in vascular biology: a view from 2013

This review considers recent developments concerning the role of integrins in vascular biology with a specific emphasis on integrin activation, and the crosstalk between integrins and growth factor receptors.

Recent studies have shown leukocytes can mediate direct transfer of molecules into endothelial cells, how specific integrins can be used to transduce signaling events, in particular in vascular beds, and how endothelial cell integrins can be targeted with specific ligands for the delivery of therapeutics. Kindlin and talin are both essential for integrin activation based on in-vivo studies of mice and humans in which the genes encoding for these proteins have been inactivated. Recent studies have attempted to translate these in-vivo realities into in-vitro models with mixed results.

Mechanisms and consequences of integrin-ligand interactions on blood and vascular cells remain a major topic of hematological research. Crucial to the ligand binding function of integrins are two intracellular binding partners, talin and kindlin. In seeking to define the molecular basis for 'integrin activation', a mechanism must be envisioned in which both proteins talin and kindlin are required to produce a productive functional response, be it platelet aggregation or leukocyte extravasation. On endothelial cells, integrins and vascular endothelial growth factor receptor 2 influence the activation of one another by virtue of their direct physical interaction. It has been shown that this bidirectional communication is subject to regulation during angiogenesis.