Vascular endothelial growth factor C induces angiogenesis in vivo

• DOI: 10.1073/pnas.95.24.14389
• Publication Date: 2002-07-26T14:40:11Z
• Authors: Yihai Cao; Philip Linden; Jacob Farnebo; Renhai Cao; Anna Eriksson; Vijay Kumar; Jian-Hua Qi; Lena Claesson-Welsh; Kari Alitalo
• Keywords: 0301 basic medicine; Neovascularization, Pathologic; Neovascularization, Physiologic; Receptor Protein-Tyrosine Kinases; Chick Embryo; Chorion; Endothelial Growth Factors; Pichia; Cornea; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Allantois; Proto-Oncogene Proteins; Animals; Humans; Fibroblast Growth Factor 2; Endothelium, Vascular; Cloning, Molecular; Aorta; Cell Division; Cell Size

Vascular endothelial growth factor C (VEGF-C) recently has been described to be a relatively specific growth factor for the lymphatic vascular 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 mouse cornea. Similar to VEGF, the angiogenic response of corneas induced by VEGF-C is intensive, with a high density of new capillaries. However, the outgrowth of microvessels stimulated by VEGF-C was significantly longer than that induced by VEGF. In the developing embryo, VEGF-C was able to induce branch sprouts from the established blood vessels. VEGF-C also induced an elongated, spindle-like cell shape change and actin reorganization in both VEGF receptor (VEGFR)-2 and VEGFR-3-overexpressing endothelial cells, but not in VEGFR-1-expressing cells. Further, both VEGFR-2 and VEGFR-3 could mediate proliferative and chemotactic responses in endothelial cells on VEGF-C stimulation. Thus, VEGF-C may regulate physiological angiogenesis and participate in the development and progression of angiogenic diseases in addition to lymphangiogenesis.