on June 2, 2005
Published online before print June 2, 2005, doi: 10.1161/01.ATV.0000172631.50972.0f
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Submitted on December 1, 2004
Accepted on May 2, 2005
Vitamin E Inhibits Abdominal Aortic Aneurysm Formation in Angiotensin II-Infused, Apolipoprotein E-Deficient Mice
Dan Gavrila ;
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; Veteran’s 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.
* To whom correspondence should be addressed. E-mail: neal-weintraub{at}uiowa.edu.
Background--Abdominal aortic aneurysms (AAAs) in humans are associated with locally increased oxidative stress and activity of NAD(P)H 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 ad 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.
Key words: aneurysm • vitamin E • oxidative stress • vascular inflammation • NADPH oxidase • osteopontin
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