VEGFR-2-specific ligand VEGF-E induces non-edematous hyper-vascularization in mice.
VEGF family members play important roles in angiogenesis and vascular permeability. VEGF-A-transgenic mice showed an increased vascularization with edema due to hyper-vascular permeability and subcutaneous hemorrhage as side effects. VEGF-A binds and activates two receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). To dissect the signals of these two receptors, we generated transgenic mice overexpressing either the VEGFR-2-specific ligand VEGF-E(NZ-7) or VEGFR-1-specific ligand PlGF-II under the control of the Keratin-14 promoter. VEGF-E-mice showed a significant increase in vascularization (about 10-fold compared to control mice) in subcutaneous tissues, whereas PlGF-mice showed only a 2-3-fold increase. Interestingly, VEGF-E-mice did not show any clear edematous lesions or hemorrhagic spots on the skin. Microscopically, VEGF-E-induced capillary networks have a well organized structure with the recruitment of pericytes. These results indicate that VEGF-E is a new angiogenic agent with less side effects for clinical usage.
Kiba
Atsushi
A
Division of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan.
Sagara
Hiroshi
H
Hara
Takeshi
T
Shibuya
Masabumi
M
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000033:anatomy & histology; D020405:Dermis / Q000033:anatomy & histology / Q000098:blood supply / Q000473:pathology; D004487:Edema / Q000378:metabolism; D006801:Humans; D053547:Keratin-14; D007633:Keratins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000235:genetics; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D019076:Transgenes; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D043925:Angiogenesis Inducing Agents; C507540:KRT14 protein, human; D053547:Keratin-14; C507446:Krt14 protein, mouse; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; C084758:VEGF-like protein, Orf virus; D014764:Viral Proteins; D000072483:Placenta Growth Factor; D007633:Keratins; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2