Dietary supplementation with vitamins C and E prevents downregulation of endothelial NOS expression in hypercholesterolemia in vivo and in vitro.
Impaired endothelium-dependent vasodilation has been associated with decreased NO bioavailability in hypercholesterolemia. This study aimed to determine whether antioxidant vitamins C and E could improve hypercholesterolemia-derived endothelial dysfunction in the porcine model, and whether observed in vivo results could be reproduced in vitro by incubation of coronary endothelial cells (EC) in the presence of native low-density lipoproteins (LDL). Adult mini-pigs were fed standard (C), cholesterol rich (HC) or cholesterol rich diet supplemented with vitamins C and E (HCV). Endothelium-dependent blood flow increase in response to acetylcholine was determined. Endothelial nitric oxide synthase (eNOS) expression was measured in arterial samples and in EC incubated with LDL isolated from porcine plasma. Vasomotor response to acetylcholine in HC was significantly lower (P<0.05) than control and HCV. There was a significant (P<0.05) decrease in eNOS immunoreactivity in HC, compared with HCV and control. Native LDL from HC, but not from HCV, induced a significant decrease in eNOS expression. Vitamins C and E treatment improved the endothelium-dependent vasomotor capacity and prevented decreased expression of eNOS in hypercholesterolemic pigs. A similar effect could be demonstrated in vitro, by incubation of EC with native LDL, suggesting that the effect of physiologically-modified LDL on eNOS could have a role in recovering vascular function.
Atherosclerosis Research Laboratory, Division of Cardiovascular Pathophysiology, School of Medicine, University of Navarra, C/Irunlarrea 1, CIFA, 31008, Pamplona, Spain
José A
JA
Rodríguez
Andrés
A
Grau
Ezequiel
E
Eguinoa
Beatriz
B
Nespereira
Maitane
M
Pérez-Ilzarbe
Roberto
R
Arias
Maria S
MS
Belzunce
José A
JA
Páramo
Diego
D
Martínez-Caro
D000704:Analysis of Variance; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology; D006937:Hypercholesterolemia / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D008297:Male; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013552:Swine; D014810:Vitamin E / Q000494:pharmacology*
D014810:Vitamin E; D019001:Nitric Oxide Synthase; D001205:Ascorbic Acid