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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1671.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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, Jr; Larry W. Oberley; Kevin C. Dellsperger; Neal L. Weintraub

From the Department of Internal Medicine (D.G., W.G.L., M.L.M., M.T., F.J.M., N.L.W.), University of Iowa, Iowa City; the Free Radical and Radiation Biology Program (M.L.M., F.J.M., L.W.O., N.L.W.), Department of Radiation Oncology, University of Iowa, Iowa City; Veterans Administration Medical Center (N.L.W.), Iowa City; the Department of Internal Medicine (A.D.), University of Kentucky, Lexington; the Graduate Center for Nutritional Sciences (L.A.C.), University of Kentucky, Lexington; and the Department of Internal Medicine (K.C.D.), University of Missouri, Columbia.

Correspondence to Dr Neal L. Weintraub, Dept of Internal Medicine, University of Iowa College of Medicine, 200 Hawkins Dr, E-329GH, Iowa City, IA 52242. E-mail neal-weintraub{at}uiowa.edu

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.

We investigated the effects of vitamin E on angiotensin II–induced abdominal aortic aneurysms (AAAs) in apolipoprotein E–deficient mice. Vitamin E reduced AAA maximal diameter and weight while attenuating aortic 8-isoprostane formation, macrophage infiltration, and osteopontin expression (P<0.05, respectively). Vitamin E also decreased the combined end point of fatal plus nonfatal artic rupture by 44% (P<0.05). Vitamin E did not affect lipid profile, systolic blood pressure, or the extent of aortic root atherosclerosis. We conclude that vitamin E inhibits AAA formation and improves clinical end points in this experimental model.

Key Words: aneurysm • vitamin E • oxidative stress • vascular inflammation • NADPH oxidase • osteopontin

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