title: Dietary ellagic acid improves oxidant-induced endothelial dysfunction and atherosclerosis: role of Nrf2 activation.
abstract: BACKGROUND
  Oxidative stress-induced vascular endothelial cell injury is a major factor in the pathogenesis of atherosclerosis. Several evidences indicate that ellagic acid (EA), a phenolic compound, contributes to cardiovascular health. This study was to investigate the effects of EA on endothelial dysfunction and atherosclerosis via antioxidant-related mechanisms.
  
  
  METHODS
  In animal studies, wild-type (WT) C57BL/6 mice and apolipoprotein E-deficient mice (ApoE(-/-)) mice were fed: a high-fat (21%) diet (HFD) or a HFD plus with EA (HFD+EA), for 14weeks. Vascular reactivity was studied in mice aortas. The effect of EA in human umbilical vein endothelial cells (HAECs) exposed to hypochlorous acid (HOCl) was also investigated.
  
  
  RESULTS
  Compared with animals on HFD alone, EA attenuated atherosclerosis in WT mice. In aortic rings from two mice models, EA significantly improved endothelium-dependent relaxation and attenuated HOCl-induced endothelial dysfunction. Besides, EA significantly improved nitric oxide synthase activity, antioxidant capacity and markers of endothelial dysfunction in plasma. Western blot analysis showed that EA increased NF-E2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) expression in the aortas (P<0.05). In a separate experiment, EA did not protect against HOCl-induced endothelial dysfunction in arteries obtained from Nrf2 gene knockout mice compared with WT mice. In HAECs, EA prevented HOCl-induced cellular damage and induced HO-1 protein expression, and these effects markedly abolished by the siRNA of Nrf2.
  
  
  CONCLUSIONS
  Our results provide further support for the protective effects of dietary EA particularly oxidant-induced endothelial dysfunction and atherosclerosis partly via Nrf2 activation.
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Beijing Institute of Biotechnology, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Biotechnology, China; Department of Health Services, Fourth Military Medical University, China.
authors.forename: KaiYuan
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: MinChun
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: MingMing
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: YanYan
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, China.
authors.forename: YuWen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, China. Electronic address: adwen-2004@hotmail.com.
authors.forename: AiDong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D004610:Ellagic Acid / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009924:Organ Culture Techniques; D016877:Oxidants / Q000633:toxicity*; D011897:Random Allocation
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D016877:Oxidants; D004610:Ellagic Acid
keywords: Atherosclerosis; Endothelial dysfunction; Oxidative stress