Stalmans, Ingeborg and Ng, Yin-Shan and Rohan, Richard and Fruttiger, Marcus and Bouché, Ann and Ÿuce, Ali and Fujisawa, Hajime and Hermans, Bart and Shani, Moshe and Jansen, Sandra and Hicklin, Dan and Anderson, David J. and Gardiner, Tom and Hammes, Hans-Peter and Moons, Lieve and Dewerchin, Mieke and Collen, Désiré and Carmeliet, Peter and D'Amore, Patricia A. (2002) Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms. Journal of Clinical Investigation, 109 (3). pp. 327-336. ISSN 0021-9738 http://resolver.caltech.edu/CaltechAUTHORS:STAjci02
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The 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.
|Additional Information:||Copyright © 2002, The American Society for Clinical Investigation. Received for publication October 9, 2001, and accepted in revised form December 27, 2001. The authors thank A. Van Lommel (Pathology Department, Catholic University Leuven) and A. Bouché, K. Vandevelde, W. Man, L. Kieckens, A. Manderveld, F. De Wever, K. Maris, T. Vancoetsem, E. Gils, K. Bijnens, A. Vandenhoeck, P. Van Wesemael, L. Godde, S. Lucas, C. Van Huylebroeck, S. Wyns (The Center for Transgene Technology and Gene Therapy, Leuven) for assistance. They acknowledge K. Alitalo for providing the Tie1 promotor. I. Stalmans is a Research Assistant of the Fonds voor Wetenschappelijk Onderzoek (FWO), Belgium and P. D’Amore is a Jules and Doris Stein Research to Prevent Blindness Professor. This work is further supported by grants from the FWO (G012500), the Geconcerteerde Onderzoeksacties Belgium (2001/09), and the European Union (BMH4-CT98-3380) to P. Carmeliet; from the NIH (HL-6221 and CA-45548) to D.J. Anderson and P. D’Amore; and from Deutsche Forschungsgemeinschaft to H.-P. Hammes.|
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