%0 Journal Article %J FASEB J %D 2002 %T Adenoviral VEGF-C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes %A Saaristo, Anne %A Veikkola, Tanja %A Enholm, Berndt %A Hytönen, Maija %A Arola, Johanna %A Pajusola, Katri %A Turunen, Païvi %A Jeltsch, Michael %A Karkkainen, Marika J %A Kerjaschki, Dontscho %A Bueler, Hansruedi %A Ylä-Herttuala, Seppo %A Alitalo, Kari %X 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. %B FASEB J %V 16 %P 1041 - 9 %8 2002/Jul/ %G eng %U http://view.ncbi.nlm.nih.gov/pubmed/12087065 %N 9 %! The FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology