VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment

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VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment

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Title: VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment
Author: Cursiefen, Claus; Chen, Lu; Borges, Leonardo P.; Jackson, David; Cao, Jingtai; Radziejewski, Czeslaw; D'Amore, Patricia Ann; Dana, Reza; Wiegand, Stanley J.; Streilein, J. Wayne

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Citation: Cursiefen, Claus, Lu Chen, Leonardo P. Borges, David Jackson, Jingtai Cao, Czeslaw Radziejewski, Patricia A. D’Amore, M. Reza Dana, Stanley J. Wiegand, and J. Wayne Streilein. 2004. “VEGF-A Stimulates Lymphangiogenesis and Hemangiogenesis in Inflammatory Neovascularization via Macrophage Recruitment.” Journal of Clinical Investigation 113 (7) (April 1): 1040–1050. doi:10.1172/jci20465.
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Abstract: Lymphangiogenesis, an important initial step in tumor metastasis and transplant sensitization, is mediated by the action of VEGF-C and -D on VEGFR3. In contrast, VEGF-A binds VEGFR1 and VEGFR2 and is an essential hemangiogenic factor. We re-evaluated the potential role of VEGF-A in lymphangiogenesis using a novel model in which both lymphangiogenesis and hemangiogenesis are induced in the normally avascular cornea. Administration of VEGF Trap, a receptor-based fusion protein that binds and neutralizes VEGF-A but not VEGF-C or -D, completely inhibited both hemangiogenesis and the outgrowth of LYVE-1+ lymphatic vessels following injury. Furthermore, both lymphangiogenesis and hemangiogenesis were significantly reduced in mice transgenic for VEGF-A164/164 or VEGF-A188/188 (each of which expresses only one of the three principle VEGF-A isoforms). Because VEGF-A is chemotactic for macrophages and we demonstrate here that macrophages in inflamed corneas release lymphangiogenic VEGF-C/VEGF-D, we evaluated the possibility that macrophage recruitment plays a role in VEGF-A–mediated lymphangiogenesis. Either systemic depletion of all bone marrow–derived cells (by irradiation) or local depletion of macrophages in the cornea (using clodronate liposomes) prior to injury significantly inhibited both hemangiogenesis and lymphangiogenesis. We conclude that VEGF-A recruitment of monocytes/macrophages plays a crucial role in inducing inflammatory neovascularization by supplying/amplifying signals essential for pathological hemangiogenesis and lymphangiogenesis.
Published Version: 10.1172/jci20465
Other Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC379325/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34388127
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