Authors:
Saaristo, A.;
Veikkola, T.;
Enholm, B.;
Hytonen, M.;
Arola, J.;
Pajusola, K.;
Turunen, P.;
Jeltsch, M.;
Karkkainen, M.J.;
Kerjaschki, D.;
Bueler, H.;
Yla-Herttuala, S.;
Alitalo, K.Source:
FASEB J, Volume 16, Issue 9, Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum, University of Helsinki and Helsinki University Central Hospital, 00014 Helsinki, Finland, p.1041-9 (2002)
URL:
http://www.fasebj.org/cgi/content/full/16/9/1041
Abstract:
Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are important regulators of blood and lymphatic vessel growth and vascular permeability. The VEGF-C/VEGFR-3 signaling pathway is crucial for lymphangiogenesis, and heterozygous inactivating missense mutations of the VEGFR-3 gene are associated with hereditary lymphedema. However, VEGF-C can have potent effects on blood vessels because its receptor VEGFR-3 is expressed in certain blood vessels and because the fully processed form of VEGF-C also binds to the VEGFR-2 of blood vessels. To characterize the in vivo effects of VEGF-C on blood and lymphatic vessels, we have overexpressed VEGF-C via adenovirus- and adeno-associated virus-mediated transfection in the skin and respiratory tract of athymic nude mice. This resulted in dose-dependent enlargement and tortuosity of veins, which, along with the collecting lymphatic vessels were found to express VEGFR-2. Expression of angiopoietin 1 blocked the increased leakiness of the blood vessels induced by VEGF-C whereas vessel enlargement and lymphangiogenesis were not affected. However, angiogenic sprouting of new blood vessels was not observed in response to AdVEGF-C or AAV-VEGF-C. These results show that virally produced VEGF-C induces blood vessel changes, including vascular leak, but its angiogenic potency is much reduced compared with VEGF in normal skin