Vitamins C and E prevent endothelial VEGF and VEGFR-2 overexpression induced by porcine hypercholesterolemic LDL
Rodríguez JA, Nespereira B, Pérez-Ilzarbe M, Eguinoa E, Páramo JA.
Atherosclerosis Research Laboratory, Division of Cardiovascular Pathophysiology, School of Medicine, Foundation for Applied Medical Research, University of Navarra, Pamplona Navarra E-31008, Spain.
Magazine: Cardiovascular Research
Date: Feb 15, 2005Hematología y Hemoterapia [SP]
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.
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.
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.
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.
CITATION Cardiovasc Res. 2005 Feb 15;65(3):665-73
you maybe interested
The Clínica is the greater private hospital with technological equipment of Spain, all in a single center.
The professionals of the Clínica perform continuous research and training, always to the benefit of the patient.
Learn why we are different from other healthcare centers. Quality, speed, comfort and results.