title: PTK7+ Mononuclear Cells Express VEGFR2 and Contribute to Vascular Stabilization by Upregulating Angiopoietin-1.
abstract: OBJECTIVE
  In angiogenesis, circulating mononuclear cells are recruited to vascular lesions; however, the underlying mechanisms are poorly understood.
  
  
  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.
authors.affiliation: From the Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA (S.K.C., H.K.L., H.S.L., E.Y.P., R.D.); Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea (H.K.L., E.J.); and Department of Ophthalmology, Seoul St. Mary's Hospital, Catholic University of Korea, Seoul, Korea (H.S.L.).
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
authors.affiliation: From the Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA (S.K.C., H.K.L., H.S.L., E.Y.P., R.D.); Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea (H.K.L., E.J.); and Department of Ophthalmology, Seoul St. Mary's Hospital, Catholic University of Korea, Seoul, Korea (H.S.L.). shadik@yuhs.ac reza_dana@meei.harvard.edu.
authors.forename: Hyung Keun
authors.initials: HK
authors.lastname: Lee
authors.affiliation: From the Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA (S.K.C., H.K.L., H.S.L., E.Y.P., R.D.); Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea (H.K.L., E.J.); and Department of Ophthalmology, Seoul St. Mary's Hospital, Catholic University of Korea, Seoul, Korea (H.S.L.).
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Lee
authors.affiliation: From the Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA (S.K.C., H.K.L., H.S.L., E.Y.P., R.D.); Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea (H.K.L., E.J.); and Department of Ophthalmology, Seoul St. Mary's Hospital, Catholic University of Korea, Seoul, Korea (H.S.L.).
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Park
authors.affiliation: From the Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA (S.K.C., H.K.L., H.S.L., E.Y.P., R.D.); Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea (H.K.L., E.J.); and Department of Ophthalmology, Seoul St. Mary's Hospital, Catholic University of Korea, Seoul, Korea (H.S.L.).
authors.forename: Eunae
authors.initials: E
authors.lastname: Jeong
authors.affiliation: From the Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA (S.K.C., H.K.L., H.S.L., E.Y.P., R.D.); Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea (H.K.L., E.J.); and Department of Ophthalmology, Seoul St. Mary's Hospital, Catholic University of Korea, Seoul, Korea (H.S.L.). shadik@yuhs.ac reza_dana@meei.harvard.edu.
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism*; D000818:Animals; D018845:CD11 Antigens; D002633:Chemotaxis; D018920:Coculture Techniques; D003315:Cornea / Q000166:cytology; D042783:Endothelial Cells / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015854:Up-Regulation; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D018845:CD11 Antigens; D016328:NF-kappa B; D012333:RNA, Messenger; C486452:Ptk7 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: PTK7 protein; VEGFR2 protein; angiopoietin-1; mouse