Polyphenol-enriched diet prevents coronary endothelial dysfunction by activating the Akt/eNOS pathway

Gemma Vilahur, Teresa Padró, Laura Casaní, Guiomar Mendieta, José A. López, Sergio Streitenberger, Lina Badimon

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    31 Citations (Scopus)


    © 2014 Sociedad Española de Cardiología. 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®; 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® 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 protein-1 expression. Pomanox® 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® 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® supplementation hinders hyperlipemia-induced coronary endothelial dysfunction by activating the Akt/endothelial nitric oxide-synthase pathway and favorably counteracting vascular inflammation and oxidative damage. Full English text available from: www.revespcardiol.org/en
    Original languageEnglish
    Pages (from-to)216-225
    JournalRevista Espanola de Cardiologia
    Issue number3
    Publication statusPublished - 1 Jan 2015


    • Endothelium
    • Nitric oxide
    • Oxidative stress
    • Polyphenol-rich diet
    • Pomegranate extract
    • Vasodilation


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