title: Vitamin E inhibits abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice.
abstract: BACKGROUND
  Abdominal aortic aneurysms (AAAs) in humans are associated with locally increased oxidative stress and activity of NADPH oxidase. We investigated the hypothesis that vitamin E, an antioxidant with documented efficacy in mice, can attenuate AAA formation during angiotensin II (Ang II) infusion in apolipoprotein E-deficient mice.
  
  
  RESULTS
  Six-month-old male apolipoprotein E-deficient mice were infused with Ang II at 1000 ng/kg per minute for 4 weeks via osmotic minipumps while consuming either a regular diet or a diet enriched with vitamin E (2 IU/g of diet). After 4 weeks, abdominal aortic weight and maximal diameter were determined, and aortic tissues were sectioned and examined using biochemical and histological techniques. Vitamin E attenuated formation of AAA, decreasing maximal aortic diameter by 24% and abdominal aortic weight by 34% (P<0.05, respectively). Importantly, animals treated with vitamin E showed a 44% reduction in the combined end point of fatal+nonfatal aortic rupture (P<0.05). Vitamin E also decreased aortic 8-isoprostane content (a marker of oxidative stress) and reduced both aortic macrophage infiltration and osteopontin expression (P<0.05, respectively). Vitamin E treatment had no significant effect on the extent of aortic root atherosclerosis, activation of matrix metalloproteinases 2 or 9, serum lipid profile, or systolic blood pressure.
  
  
  CONCLUSIONS
  Vitamin E ameliorates AAAs and reduces the combined end point of fatal+nonfatal aortic rupture in this animal model. These findings are consistent with the concept that oxidative stress plays a pivotal role in Ang II-driven AAA formation in hyperlipidemic mice.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Gavrila
authors.forename: Wei Gen
authors.initials: WG
authors.lastname: Li
authors.forename: Michael L
authors.initials: ML
authors.lastname: McCormick
authors.forename: Manesh
authors.initials: M
authors.lastname: Thomas
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Miller
authors.forename: Larry W
authors.initials: LW
authors.lastname: Oberley
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Dellsperger
authors.forename: Neal L
authors.initials: NL
authors.lastname: Weintraub
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D001019:Aortic Rupture / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D053495:Osteopontin; D018384:Oxidative Stress / Q000187:drug effects; D012795:Sialoglycoproteins / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D008055:Lipids; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D014662:Vasoconstrictor Agents; D053495:Osteopontin; D000804:Angiotensin II; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9