Abstract 197: Function of Endothelial Progenitor Cell alpha2 beta1 and alpha5 beta1 Integrins in Repair of Endothelial Barrier and Neovascularization
We addressed mechanisms by which mobilization of EPCs mediates vascular endothelial barrier repair and neovascularization. We tested the hypothesis that these processes require integrin-mediated cell adhesion to the underlying matrix. We used mouse bone marrow-derived EPCs expressing endothelial specific VE-cadherin, PECAM-1, and Flk-1 antigens. Fluorescent activated cell sorting (FACS) and Western analyses showed that EPCs predominantly expressed β1 integrins. In experiments designed to assess the functional activity of integrins in the mechanism of vascular endothelial repair and neovascularization, we observed that α2β1 and α5β1 integrins promoted EPC attachment on collagen and fibronectin matrix, and migration of EPCs in response to VEGF and bFGF. Blocking of α2β1 and α5β1 integrins with monoclonal antibodies impeded the ability of EPCs to form tube-like structures in matrigel. Thus, EPCs
express α2β1 and α5β1 integrins that are functional receptors for interactions with collagen and fibronectin
respond to agonists that mediate endothelial barrier repair and new vessel growth.
These findings suggest that EPC expression of α2β1 and α5β1 is an important determinant of adhesion of EPCs to the extracellular matrix and EPC migration, and thereby contribute to the mechanism of endothelial barrier re-annealing and neovascularization.