Dietary quercetin attenuates oxidant-induced endothelial dysfunction and atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: A critical role for heme oxygenase-1

Y. Shen, Natalie Ward, Jonathan Hodgson, Ian Puddey, Y. Wang, D. Zhang, G.J. Maghzal, R. Stocker, Kevin Croft

    Research output: Contribution to journalArticle

    94 Citations (Scopus)

    Abstract

    Several lines of evidence indicate that quercetin, a polyphenol derived in the diet from fruit and vegetables, contributes to cardiovascular health. We aimed to investigate the effects of dietary quercetin on endothelial function and atherosclerosis in mice fed a high-fat diet. Wild-type C57BL/6 (WT) and apolipoprotein E gene knockout (ApoE−/−) mice were fed: (i) a high-fat diet (HFD) or (ii) a HFD supplemented with 0.05% w/w quercetin (HFD+Q), for 14 weeks. Compared with animals fed HFD, HFD+Q attenuated atherosclerosis in ApoE−/− mice. Treatment with the HFD+Q significantly improved endothelium-dependent relaxation of aortic rings isolated from WT but not ApoE−/− mice and attenuated hypochlorous acid-induced endothelial dysfunction in aortic rings of both WT and ApoE−/− mice. Mechanistic studies revealed that HFD+Q significantly improved plasma F2-isoprostanes, 24 h urinary nitrite, and endothelial nitric oxide synthase activity, and increased heme oxygenase-1 (HO-1) protein expression in the aortas of both WT and ApoE−/− mice (P<0.05). HFD+Q also resulted in small changes in plasma cholesterol (P<0.05 in WT) and plasma triacylglycerols (P<0.05 in ApoE −/−mice). In a separate experiment, quercetin did not protect against hypochlorite-induced endothelial dysfunction in arteries obtained from heterozygous HO-1 gene knockout mice with low expression of HO-1 protein. Quercetin protects mice fed a HFD against oxidant-induced endothelial dysfunction and ApoE−/− mice against atherosclerosis. These effects are associated with improvements in nitric oxide bioavailability and are critically related to arterial induction of HO-1.
    Original languageEnglish
    Pages (from-to)908-915
    JournalFree Radical Biology and Medicine
    Volume65
    Early online date6 Sep 2013
    DOIs
    Publication statusPublished - Dec 2013

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