Vitamin E inhibits abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice

Dan Gavrila, Wei Gen Li, Michael L. McCormick, Manesh Thomas, Alan Daugherty, Lisa A. Cassis, Francis J. Miller, Larry W. Oberley, Kevin C. Dellsperger, Neal L. Weintraub

Research output: Contribution to journalArticle

130 Scopus citations

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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)1671-1677
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume25
Issue number8
DOIs
StatePublished - Aug 1 2005

Keywords

  • Aneurysm
  • NADPH oxidase
  • Osteopontin
  • Oxidative stress
  • Vascular inflammation
  • Vitamin E

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Gavrila, D., Li, W. G., McCormick, M. L., Thomas, M., Daugherty, A., Cassis, L. A., Miller, F. J., Oberley, L. W., Dellsperger, K. C., & Weintraub, N. L. (2005). Vitamin E inhibits abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice. Arteriosclerosis, thrombosis, and vascular biology, 25(8), 1671-1677. https://doi.org/10.1161/01.ATV.0000172631.50972.0f