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(-)-Epicatechin induced reversal of endothelial cell aging and improved vascular function: Underlying mechanisms

Abstract

The consumption of cacao products rich in (-)-epicatechin associates with reduced cardiovascular risk and improved vascular function. However, little is known about epicatechin effects on aged endothelium. In order to characterize the health restoring effects of epicatechin on aged endothelium and identify underlying mechanisms, we utilized high passage number (i.e. aged) bovine coronary artery endothelial cells and aortas of 3 and 18 month old rats. We evaluated cell senescence (β-galactosidase), nitric oxide (NO) production through the endothelial nitric oxide synthase pathway, mitochondria related endpoints, citrate synthase activity and vascular relaxation. Cells were treated with water or epicatechin (1 μM) for 48 h and rats orally with either water or epicatechin (1 mg/kg/day) for 15 days. Senescence associated β-galactosidase levels doubled in aged cells while those treated with epicatechin only evidenced ~40% increase. NO levels in cells decreased by ~33% with aging and epicatechin normalized them. Endothelial nitric oxide synthase phosphorylation levels paralleled these results. Aging increased total protein and synthase acetylation levels and epicatechin partially restored them to those of young by stimulating sirtuin-1 binding to the synthase. Phosphorylated sirtuin-1, mitofilin, oxidative phosphorylation complexes and transcriptional factor for mitochondria were reduced by ~40% with aging and were restored by epicatechin. Epicatechin enhanced acetylcholine induced aged aorta vasodilation and stimulated NO levels while reducing blood pressure. In conclusion, epicatechin reverses endothelial cell aging and restores key control elements of vascular function. These actions may partly explain the epidemiological evidence for the beneficial effects of cocoa consumption on the incidence of cardiac and vascular diseases.

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Publication details

The article was received on 13 Mar 2018, accepted on 27 Jul 2018 and first published on 31 Jul 2018


Article type: Paper
DOI: 10.1039/C8FO00483H
Citation: Food Funct., 2018, Accepted Manuscript
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    (-)-Epicatechin induced reversal of endothelial cell aging and improved vascular function: Underlying mechanisms

    I. Ramírez Sánchez, C. Mansour, V. Navarrete, M. Ayala, G. G. Balcazar, C. Castillo, M. L. Loredo, M. Bustamante, G. Ceballos Reyes and F. Villarreal, Food Funct., 2018, Accepted Manuscript , DOI: 10.1039/C8FO00483H

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