Abstract | BACKGROUND: 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.
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Authors | 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 |
Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 25
Issue 8
Pg. 1671-7
(Aug 2005)
ISSN: 1524-4636 [Electronic] United States |
PMID | 15933246
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antioxidants
- Apolipoproteins E
- Lipids
- Sialoglycoproteins
- Spp1 protein, mouse
- Vasoconstrictor Agents
- Osteopontin
- Angiotensin II
- Vitamin E
- 8-epi-prostaglandin F2alpha
- Dinoprost
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
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Topics |
- Angiotensin II
(pharmacology)
- Animals
- Antioxidants
(pharmacology)
- Aorta, Abdominal
(metabolism, pathology)
- Aortic Aneurysm, Abdominal
(metabolism, pathology, prevention & control)
- Aortic Rupture
(metabolism, pathology, prevention & control)
- Apolipoproteins E
(genetics)
- Blood Pressure
(drug effects)
- Dinoprost
(analogs & derivatives, metabolism)
- Hyperlipidemias
(genetics, metabolism, pathology)
- Lipids
(blood)
- Macrophages
(pathology)
- Male
- Matrix Metalloproteinase 2
(metabolism)
- Matrix Metalloproteinase 9
(metabolism)
- Mice
- Mice, Mutant Strains
- Osteopontin
- Oxidative Stress
(drug effects)
- Sialoglycoproteins
(metabolism)
- Vasoconstrictor Agents
(pharmacology)
- Vitamin E
(pharmacology)
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