Gousopoulos E Proulx ST Bachmann SB Dieterich LC Scholl J Karaman S Bianchi R Detmar M 2017 Secondary lymphedema is a common complication after cancer treatment, but the pathomechanisms underlying the disease remain unclear. Using a mouse tail lymphedema model, we found an increase in local and systemic levels of the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C and identified CD68+ macrophages as a cellular source. Surprisingly, overexpression of VEGF-C in a transgenic mouse model led to aggravation of lymphedema with increased immune cell infiltration and vascular leakage compared with wild-type littermates. Conversely, blockage of VEGF-C by overexpression of soluble VEGF receptor-3 reduced edema development, diminishing inflammation and blood vascular leakage. Similar findings were obtained in a hind limb lymph node excision lymphedema model. Flow cytometry analyses and immunofluorescence stainings in lymphedematic tissue showed that VEGF receptor-3 expression was restricted to lymphatic endothelial cells. Our data suggest that endogenous VEGF-C causes blood vascular leakage and fluid influx into the tissue, thus actively contributing to edema formation. These data may provide the basis for future clinical therapeutic approaches. application/pdf https://sonar.ch/global/documents/181324 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jid.2017.04.033 info:eu-repo/semantics/altIdentifier/pmid/28526302 info:eu-repo/semantics/openAccess The Journal of investigative dermatology. - 2017 Animals Biomarkers Cells, Cultured Disease Models, Animal Female Flow Cytometry Humans Lymphatic Vessels Lymphedema Macrophages Mice Mice, Transgenic Random Allocation Role Vascular Endothelial Growth Factor C Vascular Endothelial Growth Factor Receptor-3 An Important Role of VEGF-C in Promoting Lymphedema Development. http://purl.org/coar/resource_type/c_6501