Header

UZH-Logo

Maintenance Infos

An Important Role of VEGF-C in Promoting Lymphedema Development


Gousopoulos, Epameinondas; Proulx, Steven T; Bachmann, Samia B; Dieterich, Lothar C; Scholl, Jeannette; Karaman, Sinem; Bianchi, Roberta; Detmar, Michael (2017). An Important Role of VEGF-C in Promoting Lymphedema Development. Journal of Investigative Dermatology, 137(9):1995-2004.

Abstract

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.

Abstract

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.

Statistics

Citations

Dimensions.ai Metrics
19 citations in Web of Science®
19 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 04 Dec 2019
6 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Reconstructive Surgery
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Biochemistry
Life Sciences > Molecular Biology
Health Sciences > Dermatology
Life Sciences > Cell Biology
Language:English
Date:September 2017
Deposited On:04 Dec 2019 16:27
Last Modified:28 Jul 2020 14:15
Publisher:Elsevier
ISSN:0022-202X
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.jid.2017.04.033
PubMed ID:28526302

Download

Hybrid Open Access

Download PDF  'An Important Role of VEGF-C in Promoting Lymphedema Development'.
Preview
Content: Published Version
Filetype: PDF
Size: 2MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)