title: Specific dietary polyphenols attenuate atherosclerosis in apolipoprotein E-knockout mice by alleviating inflammation and endothelial dysfunction.
abstract: OBJECTIVE
  Animal and clinical studies have suggested that polyphenols in fruits, red wine, and tea may delay the development of atherosclerosis through their antioxidant and anti-inflammatory properties. We investigated whether individual dietary polyphenols representing different polyphenolic classes, namely quercetin (flavonol), (-)-epicatechin (flavan-3-ol), theaflavin (dimeric catechin), sesamin (lignan), or chlorogenic acid (phenolic acid), reduce atherosclerotic lesion formation in the apolipoprotein E (ApoE)(-/-) gene-knockout mouse.
  
  
  RESULTS
  Quercetin and theaflavin (64-mg/kg body mass daily) significantly attenuated atherosclerotic lesion size in the aortic sinus and thoracic aorta (P<0.05 versus ApoE(-/-) control mice). Quercetin significantly reduced aortic F(2)-isoprostane, vascular superoxide, vascular leukotriene B(4), and plasma-sP-selectin concentrations; and augmented vascular endothelial NO synthase activity, heme oxygenase-1 protein, and urinary nitrate excretion (P<0.05 versus control ApoE(-/-) mice). Theaflavin showed similar, although less extensive, significant effects. Although (-)-epicatechin significantly reduced F(2)-isoprostane, superoxide, and endothelin-1 production (P<0.05 versus control ApoE(-/-) mice), it had no significant effect on lesion size. Sesamin and chlorogenic acid treatments exerted no significant effects. Quercetin, but not (-)-epicatechin, significantly increased the expression of heme oxygenase-1 protein in lesions versus ApoE(-/-) controls.
  
  
  CONCLUSIONS
  Specific dietary polyphenols, in particular quercetin and theaflavin, may attenuate atherosclerosis in ApoE(-/-) gene-knockout mice by alleviating inflammation, improving NO bioavailability, and inducing heme oxygenase-1. These data suggest that the cardiovascular protection associated with diets rich in fruits, vegetables, and some beverages may in part be the result of flavonoids, such as quercetin.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Wai Mun
authors.initials: WM
authors.lastname: Loke
authors.forename: Julie M
authors.initials: JM
authors.lastname: Proudfoot
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Hodgson
authors.forename: Allan J
authors.initials: AJ
authors.lastname: McKinley
authors.forename: Neil
authors.initials: N
authors.lastname: Hime
authors.forename: Maria
authors.initials: M
authors.lastname: Magat
authors.forename: Roland
authors.initials: R
authors.lastname: Stocker
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Croft
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001018:Aortic Diseases / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D044946:Biflavonoids / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology; D002726:Chlorogenic Acid / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004149:Dioxoles / Q000494:pharmacology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000652:urine; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D028441:F2-Isoprostanes / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007975:Leukotriene B4 / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009573:Nitrites / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects; D019007:P-Selectin / Q000097:blood; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D059808:Polyphenols; D011794:Quercetin / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001057:Apolipoproteins E; D044946:Biflavonoids; D015415:Biomarkers; D004149:Dioxoles; D019332:Endothelin-1; D028441:F2-Isoprostanes; D005227:Fatty Acids; D005419:Flavonoids; D017705:Lignans; D008565:Membrane Proteins; D009566:Nitrates; D009573:Nitrites; D019007:P-Selectin; D010636:Phenols; D059808:Polyphenols; D013481:Superoxides; D007975:Leukotriene B4; C056068:theaflavin; D002726:Chlorogenic Acid; D009569:Nitric Oxide; D002392:Catechin; D002784:Cholesterol; D011794:Quercetin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C054125:sesamin