期刊
REVISTA ESPANOLA DE CARDIOLOGIA
卷 68, 期 3, 页码 216-225出版社
EDICIONES DOYMA S A
DOI: 10.1016/j.rec.2014.04.021
关键词
Endothelium; Polyphenol-rich diet; Pomegranate extract; Nitric oxide; Vasodilation; Oxidative stress
资金
- PNS (Programa Nacional de Salud) [SAF2013-42962-R, PNS-SAF2012-40208]
- CDTI-MINECO (Centro para el Desarrollo Tecnologico Industrial-Ministerio de Competitividad y Economia) [CEN-20101016]
- MICINN (Spain) [RyC-2009-5495]
Introduction and objectives: The Mediterranean diet, rich in polyphenols, has shown to be cardioprotective. However the mechanisms involved remain unknown. We investigated whether supplementation with a pomegranate extract rich in polyphenols renders beneficial effects on coronary function in a clinically relevant experimental model and characterized the underlying mechanisms. Methods: Pigs were fed a 10-day normocholesterolemic or hypercholesterolemic diet. Half of the animals were given a supplement of 625 mg/day of a pomegranate extract (Pomanox((R)); 200 mg punicalagins/day). Coronary responses to escalating doses of vasoactive drugs (acetylcholine, calcium ionophore, and sodium nitroprusside) and L-NG-monomethylarginine (endothelial nitric oxide-synthase inhibitor) were measured using flow Doppler. Akt/endothelial nitric oxide-synthase axis activation, monocyte chemoattractant protein-1 expression, oxidative deoxyribonucleic acid damage in the coronary artery, and lipoprotein resistance to oxidation were evaluated. Results: In dyslipidemic animals, Pomanox((R)) supplementation prevented diet-induced impairment of endothelial relaxation, reaching vasodilatory values comparable to normocholesterolemic animals upon stimulation with acetylcholine and/or calcium ionophore. These beneficial effects were associated with vascular Akt/endothelial nitric oxide-synthase activation and lower monocyte chemoattractant protein1 expression. Pomanox((R)) supplementation reduced systemic oxidative stress (higher high-density lipoprotein-antioxidant capacity and higher low-density lipoprotein resistance to oxidation) and coronary deoxyribonucleic acid damage. Normocholesterolemic animals elicited similar drug-related vasodilation regardless of Pomanox((R)) supplementation. All animals displayed a similar vasodilatory response to sodium nitroprusside and L-NG-monomethylarginine blunted all vasorelaxation responses except for sodium nitroprusside. Conclusions: Pomanox((R)) supplementation hinders hyperlipemia-induced coronary endothelial dysfunction by activating the Akt/endothelial nitric oxide-synthase pathway and favorably counteracting vascular inflammation and oxidative damage. (C) 2014 Sociedad Espan ola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.
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