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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Ciencias Cardiovasculares > Aterosclerosis e inflamación > DA - CIMA - Cardiovasculares - Aterosclerosis e inflamación - Artículos de revista >

Vitamins C and E prevent endothelial VEGF and VEGFR-2 overexpression induced by porcine hypercholesterolemic LDL
Authors: Rodriguez, J.A. (José Antonio)
Nespereira, B. (Beatriz)
Perez-Ilzarbe, M. (Maitane)
Eguinoa, E. (Ezequiel)
Paramo, J.A. (José Antonio)
Keywords: Atherosclerosis
Endothelial factors
Endothelial receptors
Growth factors
Issue Date: 2005
Publisher: Oxford University Press
Publisher version:
ISSN: 1755-3245
Citation: Rodriguez JA, Nespereira B, Perez-Ilzarbe M, Eguinoa E, Paramo JA. Vitamins C and E prevent endothelial VEGF and VEGFR-2 overexpression induced by porcine hypercholesterolemic LDL. Cardiovasc Res 2005 Feb 15;65(3):665-673.
OBJECTIVE: Vascular endothelial growth factor (VEGF) is believed to play a role in the development of atherosclerosis and has been found to be increased in hypercholesterolemia. We examined the hypothesis that endothelial VEGF and VEGF receptor-2 (VEGFR-2) expression is upregulated by hypercholesterolemic low-density lipoprotein (LDL) and, because it could be driven by oxidative stress, we tested whether vitamin C and E supplementation could modulate it. METHODS: Native LDL were characterized after isolation from adult normal (C-LDL), hypercholesterolemic (HC-LDL) and hypercholesterolemic mini-pigs receiving vitamins C and E (HCV-LDL). VEGF, VEGFR-2, HIF-1 alpha and superoxide anion (O(2)(-)) productions were measured in porcine coronary endothelial cells (ECs) incubated for 48 h with native LDL. The effect of exogenous ascorbic acid and alpha- or beta-tocopherol was also studied. RESULTS: HC-LDL, with high cholesterol (P<0.05) and reduced tocopherol/cholesterol ratio (P<0.05), increased significantly VEGF and VEGFR-2 (p<0.001) in EC, associated with higher O(2)(-) and HIF-1 alpha expression, in comparison with C-LDL and HCV-LDL. The addition of vitamin C and alpha- or beta-tocopherol to the culture medium prevented the induction of VEGF and VEGFR-2 expression by HC-LDL, both at mRNA and protein levels. CONCLUSIONS: Our data suggest HC-LDL induce endothelial VEGF and VEGFR-2 overexpression at least by increasing oxidative stress, and HIF-1 alpha is one of the signaling mechanisms involved. Prevention of VEGF and VEGFR-2 upregulation could help explain the beneficial effects of vitamins C and E in hypercholesterolemia-induced experimental atherosclerosis.
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