PTK7+ Mononuclear Cells Express VEGFR2 and Contribute to Vascular Stabilization by Upregulating Angiopoietin-1
Objective―In angiogenesis, circulating mononuclear cells are recruited to vascular lesions; however, the underlying mechanisms are poorly understood.
Approach and Results―Here, we characterize the functional role of protein tyrosine kinase 7 (PTK7)–expressing CD11b+ mononuclear cells in vitro and in vivo using a mouse model of angiogenesis. Although the frequencies of PTK7+CD11b+ cells in the bone marrow remained similar after vascular endothelial growth factor-A–induced neovascularization, we observed an 11-fold increase in the cornea. Importantly, vascular endothelial growth factor-A–induced chemotaxis of PTK7+ cells was mediated by vascular endothelial growth factor receptor 2. In a coculture with endothelial cells, PTK7+CD11b+ cells stabilized the vascular network for 2 weeks by expressing high levels of angiopoietin-1. The enhanced vascular stability was abolished by knockdown of angiopoietin-1 in PTK7+CD11b+ cells and could be restored by angiopoietin-1 treatment.
Conclusions―We conclude that PTK7 expression in perivascular mononuclear cells induces vascular endothelial growth factor receptor 2 and angiopoietin-1 expression and thus contributes to vascular stabilization in angiogenesis.
- Received December 31, 2014.
- Accepted May 1, 2015.
- © 2015 American Heart Association, Inc.