VEGF-D promotes pulmonary oedema in hyperoxic acute lung injury

Sato, Teruhiko, Paquet-Fifield, Sophie, Harris, Nicole C., Roufail, Sally, Turner, Debra J., Yuan, Yinan, Zhang, You-Fang, Fox, Stephen B., Hibbs, Margaret L., Wilkinson-Berka, Jennifer L., Williams, Richard A., Stacker, Steven A., Sly, Peter D. and Achen, Marc G. (2016) VEGF-D promotes pulmonary oedema in hyperoxic acute lung injury. Journal of Pathology, 239 2: 152-161. doi:10.1002/path.4708


Author Sato, Teruhiko
Paquet-Fifield, Sophie
Harris, Nicole C.
Roufail, Sally
Turner, Debra J.
Yuan, Yinan
Zhang, You-Fang
Fox, Stephen B.
Hibbs, Margaret L.
Wilkinson-Berka, Jennifer L.
Williams, Richard A.
Stacker, Steven A.
Sly, Peter D.
Achen, Marc G.
Title VEGF-D promotes pulmonary oedema in hyperoxic acute lung injury
Journal name Journal of Pathology   Check publisher's open access policy
ISSN 1096-9896
0022-3417
Publication date 2016-06
Year available 2016
Sub-type Article (original research)
DOI 10.1002/path.4708
Open Access Status DOI
Volume 239
Issue 2
Start page 152
End page 161
Total pages 10
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley & Sons
Collection year 2017
Language eng
Formatted abstract
Leakage of fluid from blood vessels, leading to oedema, is a key feature of many diseases including hyperoxic acute lung injury (HALI), which can occur when patients are ventilated with high concentrations of oxygen (hyperoxia). The molecular mechanisms driving vascular leak and oedema in HALI are poorly understood. VEGF-D is a protein that promotes blood vessel leak and oedema when overexpressed in tissues, but the role of endogenous VEGF-D in pathological oedema was unknown. To address these issues, we exposed Vegfd-deficient mice to hyperoxia. The resulting pulmonary oedema in Vegfd-deficient mice was substantially reduced compared to wild-type, as was the protein content of bronchoalveolar lavage fluid, consistent with reduced vascular leak. Vegf-d and its receptor Vegfr-3 were more highly expressed in lungs of hyperoxic, versus normoxic, wild-type mice, indicating that components of the Vegf-d signalling pathway are up-regulated in hyperoxia. Importantly, VEGF-D and its receptors were co-localized on blood vessels in clinical samples of human lungs exposed to hyperoxia; hence, VEGF-D may act directly on blood vessels to promote fluid leak. Our studies show that Vegf-d promotes oedema in response to hyperoxia in mice and support the hypothesis that VEGF-D signalling promotes vascular leak in human HALI.
Keyword Hyperoxia
Hyperoxic acute lung injury
Pulmonary oedema
Vascular leak
VEGF-D
VEGFR-2
VEGFR-3
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
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