Vascular endothelial growth factor C induces angiogenesis in vivo.
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.
Cao
Y
Y
Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden. yihai.cao@mtc.ki.se
Linden
P
P
Farnebo
J
J
Cao
R
R
Eriksson
A
A
Kumar
V
V
Qi
J H
JH
Claesson-Welsh
L
L
Alitalo
K
K
D000482:Allantois / Q000098:blood supply; D000818:Animals; D001011:Aorta; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply; D003001:Cloning, Molecular; D003315:Cornea / Q000098:blood supply; D016228:Endothelial Growth Factors / Q000494:pharmacology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010843:Pichia; D011518:Proto-Oncogene Proteins / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D017978:Receptors, Growth Factor / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D042582:Vascular Endothelial Growth Factor C; D040281:Vascular Endothelial Growth Factor Receptor-1; D040321:Vascular Endothelial Growth Factor Receptor-3
D016228:Endothelial Growth Factors; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D042582:Vascular Endothelial Growth Factor C; D016222:Fibroblast Growth Factor 2; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040321:Vascular Endothelial Growth Factor Receptor-3