PTK7+Mononuclear Cells Express VEGFR2 and Contribute to Vascular Stabilization by Upregulating Angiopoietin-1Significance

Abstract

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. While the frequencies of PTK7+CD11b+ cells in the bone marrow remained similar after vascular endothelial growth factor (VEGF)-A induced neovascularization, we observed an 11-fold increase in the cornea. Importantly, VEGF-A–induced chemotaxis of PTK7+ cells was mediated by VEGF receptor (VEGFR) 2. In a co-culture with endothelial cells, PTK7+CD11b+ cells stabilized the vascular network for 2 weeks by expressing high levels of angiopoietin-1 (ANG-1). The enhanced vascular stability was abolished by knockdown of ANG-1 in PTK7+CD11b+ cells and could be restored by ANG-1 treatment. Conclusions We conclude that PTK7 expression in perivascular mononuclear cells induces VEGFR2 and ANG-1 expression, and thus contributes to vascular stabilization in angiogenesis.