title: Zinc protects against diabetes-induced pathogenic changes in the aorta: roles of metallothionein and nuclear factor (erythroid-derived 2)-like 2.
abstract: BACKGROUND
  Cardiovascular diseases remain a leading cause of the mortality world-wide, which is related to several risks, including the life style change and the increased diabetes prevalence. The present study was to explore the preventive effect of zinc on the pathogenic changes in the aorta.
  
  
  METHODS
  A genetic type 1 diabetic OVE26 mouse model was used with/without zinc supplementation for 3 months. To determine gender difference either for pathogenic changes in the aorta of diabetic mice or for zinc protective effects on diabetes-induced pathogenic changes, both males and females were investigated in parallel by histopathological and immunohistochemical examinations, in combination of real-time PCR assay.
  
  
  RESULTS
  Diabetes induced significant increases in aortic oxidative damage, inflammation, and remodeling (increased fibrosis and wall thickness) without significant difference between genders. Zinc treatment of these diabetic mice for three months completely prevented the above pathogenic changes in the aorta, and also significantly up-regulated the expression and function of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a pivotal regulator of anti-oxidative mechanism, and the expression of metallothionein (MT), a potent antioxidant. There was gender difference for the protective effect of zinc against diabetes-induced pathogenic changes and the up-regulated levels of Nrf2 and MT in the aorta.
  
  
  CONCLUSIONS
  These results suggest that zinc supplementation provides a significant protection against diabetes-induced pathogenic changes in the aorta without gender difference in the type 1 diabetic mouse model. The aortic protection by zinc against diabetes-induced pathogenic changes is associated with the up-regulation of both MT and Nrf2 expression.
authors.affiliation: Department of Ophthalmology, the Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Miao
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Weixia
authors.initials: W
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.forename: Yang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Guanfang
authors.initials: G
authors.lastname: Su
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000517:prevention & control*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008668:Metallothionein / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology; D015032:Zinc / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D008668:Metallothionein; D015032:Zinc
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