Specific dietary polyphenols attenuate atherosclerosis in apolipoprotein E-knockout mice by alleviating inflammation and endothelial dysfunction.
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.
Loke
Wai Mun
WM
School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
Proudfoot
Julie M
JM
Hodgson
Jonathan M
JM
McKinley
Allan J
AJ
Hime
Neil
N
Magat
Maria
M
Stocker
Roland
R
Croft
Kevin D
KD
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
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