Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation

Carbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vei...

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Detalhes bibliográficos
Autores: Ahmad, Shakil, Hewett, Peter W., Fujisawa, Takeshi, Sissaoui, Samir, Cai, Meng, Gueron, Geraldine, Al Ani, Bahjat, Cudmore, Melissa, Faraz Ahmed, S., Wong, Michael K. K., Wegiel, Barbara, Otterbein, Leo E., Vítek, Libor, Ramma, Wenda, Wang, Keqing, Ahmed, Asif
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/36887
Acesso em linha:http://hdl.handle.net/11336/36887
Access Level:acceso abierto
Palavra-chave:Angiogenesis
Carbon Monoxide
Endothelial Cells
Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor Receptor-2
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descrição
Resumo:Carbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor- reduced Matrigel and treated with a CO-releasing molecule (CORM-2) or exposed to CO gas (250 ppm). Here, we report the surprising finding that exposure to CO inhibits vascular endothelial growth factor (VEGF)-induced endothelial cell actin reorganisation, cell proliferation, migration and capillary-like tube formation. Similarly, CO suppressed VEGF-mediated phosphorylation of VEGFR-2 at tyrosine residue 1175 and 1214 and basic fibroblast growth factor- (FGF-2) and VEGF-mediated Akt phosphorylation. Consistent with these data, mice exposed to 250 ppm CO (1h/day for 14 days) exhibited a marked decrease in FGF-2-induced Matrigel plug angiogenesis (p<0.05). These data establish a new biological function for CO in angiogenesis and point to a potential therapeutic use for CO as an anti-angiogenic agent in tumour suppression.

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