Vascular endothelial growth factor C is increased in endometrium and promotes endothelial functions, vascular permeability and angiogenesis and growth of endometriosis

Endometriosis is an angiogenesis-dependent disease. Many studies demonstrated inhibition of angiogenesis leads to inhibition of endometriotic growth, however underlying mechanism is still not fully understood. Our previous study suggested vascular endothelial growth factor C (VEGF-C) as a target of anti-angiogenesis therapy for endometriosis. In this study, VEGF-C in endometrium and its role in angiogenesis of endometriosis were studied. Human endometrium were obtained from women with and without endometriosis for molecular studies. VEGF-A, VEGF-B, VEGF-C and VEGF-D mRNA and proteins in eutopic and ectopic endometrium were measured. Human endothelial cells were transfected with VEGF-C siRNA in vitro, effects of VEGF-C on endothelial cell migration, invasion and tube formation were investigated in vitro. Angiogenesis was inhibited in wild type mice, vascular permeability in dermal skin was determined in vivo. Transplanted endometrium were inhibited by VEGF-C siRNA in immunocompromised mice, development, growth and angiogenesis of the experimental endometriosis were compared in vivo. The results showed that VEGF-C mRNA and protein were increased in eutopic and ectopic endometrium of endometriosis patients. VEGF-C siRNA significantly inhibited endothelial cell migration and tube formation. VEGF-C siRNA significantly inhibited development and angiogenesis of the experimental endometriotic lesions in mice. Supplementation and over-expression of VEGF-C significantly reversed the inhibitory effects on the endothelial functions, vascular permeability and endometriotic growth. In conclusion, VEGF-C is increased in endometrium and it promotes endothelial functions, vascular permeability and development of experimental endometriosis. VEGF-C is important for angiogenesis in endometriosis. Similar content being viewed by others

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This work was supported by the Global Scholarship Programme for Research Excellence-CNOOC grant 2008–2009 from the Chinese University of Hong Kong to H.X. and C.C.W. to conduct experiments at Harvard and Oxford Universities; an Incentive Scheme on Research Performance from the Chinese University of Hong Kong to T.Z. for PhD study; a Hong Kong Obstetrical and Gynaecological Trust Fund 2010 grant from the Obstetrical and Gynaecological Society of Hong Kong to C.C.W. and G.C.W.G.; a General Research Fund 2012/2013 (CUHK475012) from Hong Kong Research Grants Council to C.C.W, C.M.B. and A.L.K.; a MRC New Investigator Award (G0601458) and the Oxford Partnership Comprehensive Biomedical Research Centre from the Department of Health’s NIHR Biomedical Research Centres scheme to C.M.B.; a MRC Doctoral Training Account (DTA) and an Oxfordshire Health Services Research Committee Grant to K.E.M. Conflict of interest The authors declare there is no conflict of interest. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Xu, H., Zhang, T., Man, G.C.W. et al. Vascular endothelial growth factor C is increased in endometrium and promotes endothelial functions, vascular permeability and angiogenesis and growth of endometriosis. Angiogenesis 16, 541–551 (2013). https://doi.org/10.1007/s10456-013-9333-1 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s10456-013-9333-1