Retinal angiogenesis is mediated by an interaction between the angiotensin type 2 receptor, VEGF, and angiopoietin.

Sarlos, Stella; Rizkalla, Bishoy; Moravski, Christina J; Cao, Zemin; Cooper, Mark E; Wilkinson-Berka, Jennifer L

Sarlos, Stella; Rizkalla, Bishoy; Moravski, Christina J; Cao, Zemin; Cooper, Mark E; Wilkinson-Berka, Jennifer L.

Afiliación

Sarlos S; Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.

Am J Pathol ; 163(3): 879-87, 2003 Sep.

Article en En | MEDLINE | ID: mdl-12937129

RESUMEN

There is evidence that angiotensin II, vascular endothelial growth factor (VEGF), angiopoietins, and their cognate receptors participate in retinal angiogenesis. We investigated whether angiotensin type 2-receptor blockade (AT2-RB) reduces retinal angiogenesis and alters the expression of VEGF/VEGF-R2 and angiopoietin-Tie2. Retinopathy of prematurity (ROP) was induced in Sprague Dawley (SD) rats by exposure to 80% oxygen from postnatal (P) days 0 to 11, followed by 7 days in room air. ROP shams were in room air from P0-18. A group of ROP rats received the AT2-RB, PD123319, by mini-osmotic pump (5 mg/kg/day) from P11-18 (angiogenesis period). Evaluation of the retinal status of the AT2 receptor indicated that this receptor, as assessed by real-time PCR, immunohistochemistry, and in vitro autoradiography, was present in the retina, was more abundant than the AT1 receptor in the neonatal retina, and was increased in the ROP model. AT2-RB reduced retinal angiogenesis. VEGF and VEGF-R2 mRNA were increased in ROP and localized to blood vessels, ganglion cells, and the inner nuclear layer, and were decreased by PD123319. Angiopoietin2 and Tie2, but not angiopoietin1 mRNA were increased with ROP, and angiopoietin2 was reduced with PD123319. This study has identified a potential retinoprotective role for AT2-RB possibly mediated via interactions with VEGF- and angiopoietin-dependent pathways.

Asunto(s)

Inductores de la Angiogénesis/metabolismo; Factores de Crecimiento Endotelial/metabolismo; Péptidos y Proteínas de Señalización Intercelular/metabolismo; Linfocinas/metabolismo; Neovascularización Patológica/fisiopatología; Receptores de Angiotensina/metabolismo; Enfermedades de la Retina/fisiopatología; Vasos Retinianos/fisiopatología; Envejecimiento/metabolismo; Angiopoyetina 2; Animales; Animales Recién Nacidos; Autorradiografía; Sistemas de Computación; Factores de Crecimiento Endotelial/genética; Inmunohistoquímica; Hibridación in Situ; Péptidos y Proteínas de Señalización Intercelular/genética; Linfocinas/genética; Neovascularización Patológica/patología; Oxígeno; Reacción en Cadena de la Polimerasa; ARN Mensajero/metabolismo; Ratas; Ratas Sprague-Dawley; Receptor de Angiotensina Tipo 1; Receptor de Angiotensina Tipo 2; Retina/metabolismo; Enfermedades de la Retina/inducido químicamente; Enfermedades de la Retina/patología; Vasos Retinianos/patología; Factor A de Crecimiento Endotelial Vascular; Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética; Factores de Crecimiento Endotelial Vascular

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades de la Retina / Vasos Retinianos / Receptores de Angiotensina / Factores de Crecimiento Endotelial / Linfocinas / Péptidos y Proteínas de Señalización Intercelular / Inductores de la Angiogénesis / Neovascularización Patológica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Am J Pathol Año: 2003 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos

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