%0 Journal Article %J Circ Res %D 2001 %T Adenoviral expression of vascular endothelial growth factor-C induces lymphangiogenesis in the skin %A Enholm, B %A Karpanen, T %A Jeltsch, M %A Kubo, H %A Stenback, F %A Prevo, R %A Jackson, D G %A Yla-Herttuala, S %A Alitalo, K %X The growth of blood and lymphatic vasculature is mediated in part by secreted polypeptides of the vascular endothelial growth factor (VEGF) family. The prototype VEGF binds VEGF receptor (VEGFR)-1 and VEGFR-2 and is angiogenic, whereas VEGF-C, which binds to VEGFR-2 and VEGFR-3, is either angiogenic or lymphangiogenic in different assays. We used an adenoviral gene transfer approach to compare the effects of these growth factors in adult mice. Recombinant adenoviruses encoding human VEGF-C or VEGF were injected subcutaneously into C57Bl6 mice or into the ears of nude mice. Immunohistochemical analysis showed that VEGF-C upregulated VEGFR-2 and VEGFR-3 expression and VEGF upregulated VEGFR-2 expression at 4 days after injection. After 2 weeks, histochemical and immunohistochemical analysis, including staining for the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), the vascular endothelial marker platelet-endothelial cell adhesion molecule-1 (PECAM-1), and the proliferating cell nuclear antigen (PCNA) revealed that VEGF-C induced mainly lymphangiogenesis in contrast to VEGF, which induced only angiogenesis. These results have significant implications in the planning of gene therapy using these growth factors. %B Circ Res %V 88 %P 623 - 9 %8 2001/Mar/ %G eng %U http://view.ncbi.nlm.nih.gov/pubmed/11282897 %N 6 %! Circulation Research