VASCULAR ENDOTHELIAL GROWTH-FACTOR-C INDUCES ANGIOGENESIS IN-VIVO

Vascular endothelial growth factor C (VEGF-C) recently has been descri bed to be a relatively specific growth factor for the lymphatic vascul ar system. Here we report that ectopic application of recombinant VEGF -C also has potent angiogenic effects in vivo. VEGF-C is sufficiently potent to stimulate neovascularization from limbal vessels in the mous e cornea. Similar to VEGF, the angiogenic response of corneas induced by VEGF-C is intensive, with a high density of new capillaries. Howeve r, the outgrowth of microvessels stimulated by VEGF-C was significantl y longer than that induced by VEGF. In the developing embryo, VEGF-C w as able to induce branch sprouts from the established blood vessels. V EGF-C also induced an elongated, spindle-like cell shape change and ac tin reorganization in both VEGF receptor (VEGFR)-2 and VEGFR-3-overexp ressing endothelial cells, but not in VEGFR-1-expressing cells. Furthe r, both VEGFR-2 and VEGFR-3 could mediate proliferative and chemotacti c responses in endothelial cells on VEGF-C stimulation. Thus, VEGF-C m ay regulate physiological angiogenesis and participate in the developm ent and progression of angiogenic diseases in addition to lymphangioge nesis.