Vitamins C and E downregulate vascular VEGF and VEGFR-2 expression in apolipoprotein-E-deficient mice

Anti-angiogenic therapy reduces both plaque growth and intimal neovascularization in apolipoprotein-E-deficient mice (apoE-/-). Vascular endothelial growth factor (VEGF) has been suggested as playing a role in the development of atherosclerosis. We examined the hypothesis that VEGF and VEGF receptor...

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Detalles Bibliográficos
Autores: Nespereira, B. (Beatriz)|||/items/292b11c9-c1f3-454d-84c4-fe2b04bb275a, Perez-Ilzarbe, M. (Maitane)|||/items/e337ae1b-d63e-44a6-a819-2f3aa71900c6, Fernandez-Robredo, P. (Patricia)|||/items/cebb4451-3415-44cf-811a-c5ae0b139604, Fuentes, A.M. (Ángela M.)|||/items/4ef6118a-576c-4545-997e-bbe5cd7a1446, Páramo-Fernández, J.A. (José Antonio)|||/items/8c56baa6-2a43-4836-b91b-4eed15be3c96, Rodriguez, J.A. (José Antonio)|||/items/dfeeb791-bd5d-4472-bce8-b7f54cdf8f31
Tipo de recurso: artículo
Fecha de publicación:2003
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/22258
Acceso en línea:https://hdl.handle.net/10171/22258
Access Level:acceso abierto
Palabra clave:VEGF
VEGFR-2
Hypercholesterolemia
Ascorbic acid
Tocopherol
Descripción
Sumario:Anti-angiogenic therapy reduces both plaque growth and intimal neovascularization in apolipoprotein-E-deficient mice (apoE-/-). Vascular endothelial growth factor (VEGF) has been suggested as playing a role in the development of atherosclerosis. We examined the hypothesis that VEGF and VEGF receptor-2 (VEGFR-2) expression is upregulated in apoE-/- and, since it could be driven by oxidative stress, tested whether dietary supplementation with vitamins C and E could downregulate it.Two-month-old apoE-/- received vitamin C combined with alpha- or beta-tocopherol for 4 weeks. Aortic VEGF and VEGFR-2 expression were measured by RT-qPCR and western blot.ApoE-/- showed significantly higher expression of aortic VEGF and VEGFR-2 mRNA (P<0.001) and protein (P<0.001) than wild-type mice, as well as increased plasma VEGF (P<0.001). Vitamin C and alpha-tocopherol significantly reduced aortic VEGF and VEGFR-2 expression in apoE-/- (P<0.001), circulating VEGF (P<0.01) and plasma lipid peroxidation (P<0.01). apoE-/- receiving vitamin C and beta-tocopherol showed diminished lipid peroxidation and VEGFR-2, but only partial reduction of VEGF expression. These data demonstrate that augmented VEGF and VEGFR-2 expression in apoE-/- vasculature can be downregulated by vitamins C and E, at least partially through oxidative stress reduction. This novel mechanism could contribute to explaining the beneficial effects of antioxidant vitamins in experimental atherosclerosis.

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