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

Free Radic Biol Med. 2013 Dec;65:908-915. doi: 10.1016/j.freeradbiomed.2013.08.185. Epub 2013 Sep 7.


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.

Keywords: 1,1-diethyl-2-hydroxy-2-nitroso-hydrazine; ACh; ApoE(−/−); Atherosclerosis; DEANO; Endothelial function; Flavonoid; HAEC; HFD; HO-1; HOCl; NO; Oxidative stress; Polyphenol; Q; Quercetin; ROS; WT; acetylcholine; apolipoprotein E gene knockout; heme oxygenase-1; high-fat diet; human aortic endothelial cells; hypocholorous acid; nitric oxide; quercetin; reactive oxygen species; wild-type.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / pharmacokinetics
  • Aorta / enzymology
  • Atherosclerosis / enzymology
  • Atherosclerosis / etiology
  • Atherosclerosis / pathology
  • Cells, Cultured
  • Cholesterol / blood
  • Diet, High-Fat / adverse effects
  • Endothelium, Vascular / enzymology*
  • Endothelium, Vascular / pathology
  • Enzyme Induction
  • Female
  • Heme Oxygenase-1 / physiology*
  • Humans
  • Male
  • Membrane Proteins / physiology*
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide Synthase / metabolism
  • Oxidants / pharmacology
  • Oxidative Stress
  • Quercetin / administration & dosage*
  • Quercetin / pharmacokinetics


  • Antioxidants
  • Membrane Proteins
  • Oxidants
  • Cholesterol
  • Quercetin
  • Nitric Oxide Synthase
  • Heme Oxygenase-1
  • Hmox1 protein, mouse