Vascular Endothelial Growth Factor E (VEGFE)

Both VEGF-A and Orf-virus-encoded VEGF-E bind and activate VEGFR2; however, only VEGF-A binds VEGFR-1. Keratin-14-promoterdriven VEGF-E transgenic mice showed a significant increase in mature blood vessels. However, K14–VEGF-A transgenic mice exhibited severe inflammation and oedema with increased angiogenesis, as well as lymphangiogenesis and lymph vessel dilatation. K14–VEGF-A transgenic mice deficient in VEGFR-1 signalling showed decreases in oedema and inflammation with less recruitment of macrophage-lineage cells, suggesting an involvement of VEGFR-1 in these adverse effects. VEGFE might be more useful than VEGFA for proangiogenic therapy. The VEGFE gene is not present in the human genome, suggesting that a progenitor of the Orf virus may have captured an original VEGFE gene from the genome of an animal, probably an animal other than a mammal, by recombination.