Sunil K Chauhan1, Hyung Keun Lee2, Hyun Soo Lee1, Eun Young Park1, Eunae Jeong1, Reza Dana2. 1. 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.). 2. 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.
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. 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.
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.
Authors: Alma Zernecke; Andreas Schober; Ilze Bot; Philipp von Hundelshausen; Elisa A Liehn; Barbara Möpps; Mathias Mericskay; Peter Gierschik; Erik A Biessen; Christian Weber Journal: Circ Res Date: 2005-03-10 Impact factor: 17.367
Authors: Gavin Thurston; Quan Wang; Fabienne Baffert; John Rudge; Nicholas Papadopoulos; Danielle Jean-Guillaume; Stanley Wiegand; George D Yancopoulos; Donald M McDonald Journal: Development Date: 2005-06-15 Impact factor: 6.868
Authors: Tibor Ziegelhoeffer; Borja Fernandez; Sawa Kostin; Matthias Heil; Robert Voswinckel; Armin Helisch; Wolfgang Schaper Journal: Circ Res Date: 2003-12-04 Impact factor: 17.367
Authors: Xiaowei Lu; Annette G M Borchers; Christine Jolicoeur; Helen Rayburn; Julie C Baker; Marc Tessier-Lavigne Journal: Nature Date: 2004-07-01 Impact factor: 49.962
Authors: Q Shi; S Rafii; M H Wu; E S Wijelath; C Yu; A Ishida; Y Fujita; S Kothari; R Mohle; L R Sauvage; M A Moore; R F Storb; W P Hammond Journal: Blood Date: 1998-07-15 Impact factor: 22.113
Authors: Michele De Palma; Mary Anna Venneri; Rossella Galli; Lucia Sergi Sergi; Letterio S Politi; Maurilio Sampaolesi; Luigi Naldini Journal: Cancer Cell Date: 2005-09 Impact factor: 31.743
Authors: Tabea Osthues; Béla Zimmer; Vittoria Rimola; Kevin Klann; Karin Schilling; Praveen Mathoor; Carlo Angioni; Andreas Weigert; Gerd Geisslinger; Christian Münch; Klaus Scholich; Marco Sisignano Journal: Cells Date: 2020-07-21 Impact factor: 6.600