| Abstract | BACKGROUND: A growing body of evidence from animal studies supports the hypothesis that oxidative stress-mediated mechanisms play a central role in early atherogenesis. In contrast, clinical trials with antioxidant vitamins have not produced consistent results in humans with established atherosclerosis. METHODS AND RESULTS: Low-density lipoprotein receptor-deficient mice (LDLR KO) were fed a high-fat diet for 3 months to induce atheroma. At this time, 1 group of mice was euthanized for examination of atherosclerosis, and 2 other groups were randomized to receive high-fat diet either alone or supplemented with vitamin E for 3 additional months. At the end of the study, LDLR KO on a vitamin E-supplemented fat diet had decreased 8,12-iso-isoprostane (iP)F(2alpha)-VI and monocyte chemoattractant protein-1 levels, but increased nitric oxide levels compared with mice on placebo. No difference in lipid levels was observed between the 2 groups. Compared with baseline, placebo group had progression of atherosclerosis. In contrast, vitamin E-treated animals showed a significant reduction in progression of atherosclerosis. CONCLUSIONS: These results demonstrate that in LDLR KO, vitamin E supplementation reduces progression of established atherosclerosis by suppressing oxidative and inflammatory reactions and increasing nitric oxide levels. |
| Authors | Tillmann Cyrus, Yuemang Yao, Joshua Rokach, Lina X Tang, Domenico Praticò
(Affiliation: Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia, Pa 19104, USA.)
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| Journal | Circulation
(Circulation)
Vol. 107
Issue 4
Pg. 521-3
(Feb 4 2003)
ISSN: 1524-4539 United States |
| PMID | 12566360
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- 8,12-iso-isoprostane F2alpha-VI
- Biological Markers
- Dietary Fats
- Receptors, LDL
- Triglycerides
- Nitric Oxide
- Vitamin E
- Dinoprost
- Cholesterol
|
| Topics |
- Animals
- Aorta
(drug effects, pathology)
- Arteriosclerosis
(drug therapy, pathology)
- Biological Markers
(blood)
- Cholesterol
(blood)
- Dietary Fats
(adverse effects)
- Dietary Supplements
- Dinoprost
(analogs & derivatives, blood)
- Disease Progression
- Immunohistochemistry
- Lipid Peroxidation
(drug effects)
- Mice
- Mice, Knockout
- Nitric Oxide
(metabolism)
- Receptors, LDL
(deficiency, genetics)
- Treatment Outcome
- Triglycerides
(blood)
- Vitamin E
(blood, therapeutic use)
|
