Ingeborg Stalmans, Yin-Shan Ng, Richard Rohan, Marcus Fruttiger, Ann Bouché, Ali Ÿuce, Hajime Fujisawa, Bart Hermans, Moshe Shani, Sandra Jansen, Dan Hicklin, David J. Anderson, Tom Gardiner, Hans-Peter Hammes, Lieve Moons, Mieke Dewerchin, Désiré Collen, Peter Carmeliet, Patricia A. D’Amore
J Clin Invest.
2002;
109(3):327–336
doi:10.1172/JCI14362
This article Copyright © 2002, The American Society for Clinical Investigation
Abstract
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T
he murine VEGF gene is alternatively transcribed to yield the VEGF120, VEGF164, and VEGF188 isoforms, which differ in their potential to bind to heparan sulfate and neuropilin-1 and to stimulate endothelial growth. Here, their role in retinal vascular development was studied in mice selectively expressing single isoforms. VEGF164/164 mice were normal, healthy, and had normal retinal angiogenesis. In contrast, VEGF120/120 mice exhibited severe defects in vascular outgrowth and patterning, whereas VEGF188/188 mice displayed normal venular outgrowth but impaired arterial development. It is noteworthy that neuropilin-1, a receptor for VEGF164, was predominantly expressed in retinal arterioles. These findings reveal distinct roles of the various VEGF isoforms in vascular patterning and arterial development in the retina.
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