title: Polyphenol-enriched diet prevents coronary endothelial dysfunction by activating the Akt/eNOS pathway.
abstract: OBJECTIVE
  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.
authors.affiliation: Centro de Investigación Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Vilahur
authors.affiliation: Centro de Investigación Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Padró
authors.affiliation: Centro de Investigación Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Casaní
authors.affiliation: Centro de Investigación Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.
authors.forename: Guiomar
authors.initials: G
authors.lastname: Mendieta
authors.affiliation: Probelte Biotecnología, S.L., Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: López
authors.affiliation: Probelte Biotecnología, S.L., Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Streitenberger
authors.affiliation: Centro de Investigación Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain; Cátedra de Investigación Cardiovascular, Universidad Autónoma de Barcelona, Barcelona, Spain. Electronic address: lbadimon@csic-iccc.org.
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003324:Coronary Artery Disease / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology; D003331:Coronary Vessels / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D004247:DNA / Q000235:genetics; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000235:genetics*; D059808:Polyphenols / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D013552:Swine; D014664:Vasodilation / Q000502:physiology*
chemical_list: D059808:Polyphenols; D004247:DNA; D052250:Nitric Oxide Synthase Type III
keywords: Dieta rica en polifenoles; Endotelio; Endothelium; Estrés oxidativo; Extracto de granada; Nitric oxide; Oxidative stress; Polyphenol-rich diet; Pomegranate extract; Vasodilatación; Vasodilation; Óxido nítrico