Loss of the VEGF(164) and VEGF(188) isoforms impairs postnatal glomerular angiogenesis and renal arteriogenesis in mice.
Vascular endothelial growth factor (VEGF) is transcribed in the VEGF(120), VEGF(164), or VEGF(188) isoforms, which differ in receptor binding, matrix association, and angiogenic activity. This vascular growth factor has been implicated in the development of the renal vasculature, but the role of the distinct VEGF isoforms remains unknown. In the present report, renal angiogenesis and arteriogenesis were studied in VEGF(120/120) mice, expressing only the short VEGF(120) isoform. In VEGF(120/120) mice, ingrowth and survival of capillaries in glomeruli, remodeling of peritubular capillaries, vascular coverage by pericytes, and branching of renal arteries were all severely impaired, causing abnormal glomerular filtration and impairing renal function. The arterial branching defect might be related to a reduced expression of renin, a presumed renal arterial branching factor. Glomerulosclerosis and tubular dilation possibly resulted from renal ischemia caused by vascular defects. Thus, VEGF(164) and VEGF(188) not only mediate angiogenesis, but they also play an essential role in renal branching arteriogenesis.
Mattot
Virginie
V
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Belgium.
Moons
Lieve
L
Lupu
Florea
F
Chernavvsky
Daniel
D
Gómez
R Ariel
RA
Collen
Désiré
D
Carmeliet
Peter
P
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002196:Capillaries / Q000254:growth & development; D002454:Cell Differentiation; D016228:Endothelial Growth Factors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005919:Glomerular Filtration Rate; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D007668:Kidney / Q000254:growth & development / Q000473:pathology / Q000648:ultrastructure; D007678:Kidney Glomerulus / Q000098:blood supply*; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D018919:Neovascularization, Physiologic; D020033:Protein Isoforms; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis; D012077:Renal Artery / Q000254:growth & development*; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D042442:Vascular Endothelial Growth Factors
D018952:Antigens, CD34; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020797:Receptor, Platelet-Derived Growth Factor beta; D040301:Vascular Endothelial Growth Factor Receptor-2