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Citations to this article

VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment
Claus Cursiefen, … , Stanley J. Wiegand, J. Wayne Streilein
Claus Cursiefen, … , Stanley J. Wiegand, J. Wayne Streilein
Published April 1, 2004
Citation Information: J Clin Invest. 2004;113(7):1040-1050. https://doi.org/10.1172/JCI20465.
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Article Oncology Article has an altmetric score of 15

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

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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.

Authors

Claus Cursiefen, Lu Chen, Leonardo P. Borges, David Jackson, Jingtai Cao, Czeslaw Radziejewski, Patricia A. D’Amore, M. Reza Dana, Stanley J. Wiegand, J. Wayne Streilein

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 Total
Citations: 11 30 16 25 31 29 26 22 30 26 18 35 23 20 30 25 23 11 15 10 10 2 468
Citation information
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Citations to this article in year 2017 (30)

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Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency
D Hos, A Bukowiecki, J Horstmann, F Bock, F Bucher, LM Heindl, S Siebelmann, P Steven, R Dana, SA Eming, C Cursiefen
Scientific Reports 2017
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TK Park, SH Lee, JS Choi, SK Nah, HJ Kim, HY Park, H Lee, SH Lee, K Park
Molecular Therapy - Nucleic Acids 2017
Lymphangiogenesis guidance by paracrine and pericellular factors
K Vaahtomeri, S Karaman, T Mäkinen, K Alitalo
Genes & development 2017
Deregulated angiogenesis in chronic lung diseases: a possible role for lung mesenchymal progenitor cells (2017 Grover Conference Series)
JA Kropski, BW Richmond, CF Gaskill, RF Foronjy, SM Majka
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SN Syed, M Jung, A Weigert, B Brüne
Mediators of Inflammation 2017
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HR Gurung, MM Carr, K Bryant, AJ Chucair-Elliott, DJ Carr
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JC Gardenier, RP Kataru, GE Hespe, IL Savetsky, JS Torrisi, GD Nores, DK Jowhar, MD Nitti, RC Schofield, DC Carlow, BJ Mehrara
Nature Communications 2017
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T Lin, L Gong
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Pflügers Archiv - European Journal of Physiology 2017
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Pflügers Archiv - European Journal of Physiology 2017
Kinetics of Angiogenic Responses in Corneal Transplantation:
T Inomata, A Mashaghi, AD Zazzo, SM Lee, H Chiang, R Dana
Cornea 2017
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S Rezzola, M Corsini, P Chiodelli, A Cancarini, IM Nawaz, D Coltrini, S Mitola, R Ronca, M Belleri, L Lista, D Rusciano, MD Rosa, V Pavone, F Semeraro, M Presta
Diabetologia 2017
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NJ Reyes, EG O'Koren, DR Saban
Nature Reviews Immunology 2017
Proangiogenic Function of T Cells in Corneal Transplantation:
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Transplantation 2017
Emerging evidence for the role of differential tumor microenvironment in breast cancer racial disparity: a closer look at the surroundings
SK Deshmukh, SK Srivastava, N Tyagi, A Ahmad, AP Singh, AA Ghadhban, DL Dyess, JE Carter, K Dugger, S Singh
Carcinogenesis 2017
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M Klingeborn, WM Dismuke, CB Rickman, WD Stamer
Progress in Retinal and Eye Research 2017
Model of Vascular Desmoplastic Multispecies Tumor Growth
CF Ng, HB Frieboes
Journal of Theoretical Biology 2017
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A Bukowiecki, D Hos, C Cursiefen, S Eming
International journal of molecular sciences 2017
Blockade of MMP-2 and MMP-9 inhibits corneal lymphangiogenesis
HT Du, LL Du, XL Tang, HY Ge, P Liu
Graefe's Archive for Clinical and Experimental Ophthalmology 2017
Inhibition of HUVEC tube formation via suppression of NFκB suggests an anti-angiogenic role for SLURP1 in the transparent cornea
S Swamynathan, CL Loughner, SK Swamynathan
Experimental Eye Research 2017
Mycobacterium bovis Bacillus Calmette–Guérin Alters Melanoma Microenvironment Favoring Antitumor T Cell Responses and Improving M2 Macrophage Function
RD Lardone, AA Chan, AF Lee, LJ Foshag, MB Faries, PA Sieling, DJ Lee
Frontiers in immunology 2017
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S Ran, A Wilber
Journal of leukocyte biology 2017
Effects of proton versus photon irradiation on (lymph)angiogenic, inflammatory, proliferative and anti-tumor immune responses in head and neck squamous cell carcinoma
M Lupu-Plesu, A Claren, S Martial, PD N'Diaye, K Lebrigand, N Pons, D Ambrosetti, I Peyrottes, J Feuillade, J Hérault, M Dufies, J Doyen, G Pagès
Oncogenesis 2017
Fibroblasts: the unknown sentinels eliciting immune responses against microorganisms
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European Journal of Microbiology and Immunology 2017
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S Fertsch, M Hagouan, B Munder, T Schulz, A Abu-Ghazaleh, J Schaberick, P Stambera, M Aldeeri, C Andree, OC Thamm
Gland Surgery 2017
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Y Wu, C Xue, Y Lu, Z Huang
Indian journal of ophthalmology 2017
Therapeutic approaches for corneal neovascularization
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Eye and Vision 2017
HIF1 α -Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages
T Wang, H Liu, G Lian, SY Zhang, X Wang, C Jiang
Mediators of Inflammation 2017
Efficacy and safety of ranibizumab for wet age-related macular degeneration in Chinese patients.
Qi HJ, Li XX, Zhang JY, Zhao MW
International Journal of Ophthalmology 2017
Blockade of angiopoietin-2/Tie2 signaling pathway specifically promotes inflammation-induced angiogenesis in mouse cornea.
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International Journal of Ophthalmology 2017

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