- Title
- 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
- Creator
- Shen, Yu; Ward, Natalie; Hodgson, Jonathan; Puddey, Ian; Wang, Yutang; Zhang, Di; Maghzal, Ghassan; Stocker, Roland; Croft, Kevin
- Date
- 2013
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/167857
- Identifier
- vital:13749
- Identifier
-
https://doi.org/10.1016/j.freeradbiomed.2013.08.185
- Identifier
- ISBN:0891-5849
- 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, 24h 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. •Quercetin is an important dietary flavonoid that can reduce atherosclerosis in animal models.•Dietary quercetin improved oxidant-induced vascular dysfunction in mice.•Quercetin reduced oxidative stress, increased endothelial eNOS activity, and increased heme oxygenase-1 protein expression in aortic tissue.•Protection against oxidant-induced vascular dysfunction was critically related to arterial induction of HO-1 expression.
- Relation
- Free Radical Biology and Medicine Vol. 65, no. (2013), p. 908-915
- Rights
- Copyright Elsevier
- Rights
- This metadata is freely available under a CCO license
- Subject
- Polyphenol; Flavonoid; Quercetin; Endothelial Function; Atherosclerosis; Oxidative Stress; 0304 Medicinal and Biomolecular Chemistry; 0601 Biochemistry and cell biology
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