Junctional Adhesion Molecule A Expressed on Human CD34 + Cells Promotes Adhesion on Vascular Wall and Differentiation Into Endothelial Progenitor Cells
You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
Junctional Adhesion Molecule A Expressed on Human CD34 + Cells Promotes Adhesion on Vascular Wall and Differentiation Into Endothelial Progenitor Cells
Published in:
Arteriosclerosis, Thrombosis, and Vascular Biology, 30 (2010) 6, Seite 1127-1136
Language:
English
DOI:
10.1161/atvbaha.110.204370
ISSN:
1524-4636;
1079-5642
Origination:
Footnote:
Description:
Objective— To investigate the role of junctional adhesion molecule A (JAM-A) on adhesion and differentiation of human CD34 + cells into endothelial progenitor cells. Methods and Results— Tissue healing and vascular regeneration is a multistep process requiring firm adhesion of circulating progenitor cells to the vascular wall and their further differentiation into endothelial cells. The role of JAM-A in platelet-mediated adhesion of progenitor cells was investigated by adhesion assays in vitro and with the help of intravital fluorescence microscopy in mice. Preincubation of human CD34 + progenitor cells with soluble JAM-A-Fc (sJAM-A-Fc) resulted in significantly decreased adhesion over immobilized platelets or inflammatory endothelium under high shear stress in vitro and after carotid ligation in vivo or ischemia/reperfusion injury in the microcirculation of mice. Human CD34 + cells express JAM-A, as defined by flow cytometry and Western blot analysis. JAM-A mediates differentiation of CD34 + cells to endothelial progenitor cells and facilitates CD34 + cell-induced reendothelialization in vitro. Pretreatment of human CD34 + cells with sJAM-A-Fc resulted in increased neointima formation 3 weeks after endothelial denudation in the carotid arteries of nonobese diabetic/severe combined immunodeficient mice. Conclusion— These results indicate that the expression of JAM-A on CD34 + cells mediates adhesion to the vascular wall after injury and differentiation into endothelial progenitor cells, a mechanism potentially involved in vascular regeneration. Human CD34 + cells express JAM-A, mediating their interaction with platelets and endothelial cells. Specifically, JAM-A expressed on human CD34 + progenitor cells regulates their adhesion over immobilized platelets or inflammatory endothelium under high shear stress in vitro and after carotid ligation in vivo or ischemia/reperfusion injury in the microcirculation of mice. Moreover, it mediates differentiation of CD34 + cells to endothelial progenitor cells and facilitates reendothelialization.