title: Effect of tocopherol on atherosclerosis, vascular function, and inflammation in apolipoprotein E knockout mice with subtotal nephrectomy.
abstract: OBJECTIVE
  Inflammation and endothelial dysfunction contribute to cardiovascular disease, prevalent in chronic kidney disease (CKD). Antioxidant supplements such as tocopherols may reduce inflammation and atherosclerosis. This study aimed to investigate the effect of tocopherol supplementation on vascular function, aortic plaque formation, and inflammation in apolipoprotein E(-/-) mice with 5/6 nephrectomy as a model of combined cardiovascular and kidney disease.
  
  
  METHODS
  Nephrectomized mice were assigned to a normal chow diet group (normal chow), a group receiving 1000 mg/kg diet of α-tocopherol supplementation or a group receiving 1000 mg/kg diet mixed-tocopherol (60% γ-tocopherol).
  
  
  RESULTS
  Following 12 weeks, in vitro aortic endothelial-independent relaxation was enhanced with both α-tocopherol and mixed-tocopherol (P < 0.05), while mixed-tocopherol enhanced aortic contraction at noradrenaline concentrations of 3 × 10(-7) M to 3 × 10(-5) M (P < 0.05), when compared to normal chow. Supplementation with α- and mixed-tocopherol reduced systemic concentrations of IL-6 (P < 0.001 and P < 0.001, respectively) and IL-10 (P < 0.05 and P < 0.001, respectively), while α-tocopherol also reduced MCP-1 (P < 0.05) and tumor necrosis factor (TNF)-α (P < 0.05). Aortic sinus plaque area was significantly reduced with α-tocopherol supplementation when compared to normal chow (P < 0.01).
  
  
  CONCLUSIONS
  Tocopherol supplementation favorably influenced vascular function and cytokine profile, while it was also effective in reducing atherosclerosis in the apolipoprotein E(-/-) mouse with CKD.
authors.affiliation: School of Health Sciences, University of Tasmania, Launceston, Tas., Australia.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Shing
authors.forename: Robert G
authors.initials: RG
authors.lastname: Fassett
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Peake
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Coombes
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000502:physiology*; D050197:Atherosclerosis / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology*; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009392:Nephrectomy; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D013482:Superoxide Dismutase / Q000378:metabolism; D024505:Tocopherols / Q000627:therapeutic use*; D014664:Vasodilation
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D016207:Cytokines; D013482:Superoxide Dismutase; D024505:Tocopherols
keywords: Cardiovascular disease; Chronic kidney disease; Cytokines; Plaque; Tocopherol