Iron-Deficient Diet Reduces Atherosclerotic Lesions in ApoE-Deficient Mice
Abstract
Background—Iron deposition is evident in human atherosclerotic lesions, suggesting that iron may play a role in the development of atherosclerosis. To test this idea, the correlation between the extent of iron deposition and the severity of atherosclerosis in apolipoprotein E (apoE)-deficient mice was investigated. Furthermore, the effect of a low-iron diet on the progression of atherosclerotic lesions in these animals was evaluated. Methods and Results—Iron deposition in tissues of apoE-deficient mice was examined by Perls’ staining method. The results clearly demonstrated that iron deposits are present in atherosclerotic lesions and tissue sections of heart and liver in an age-dependent manner. When the young mice received a low-iron diet for 3 months, the hematocrit, serum iron, hemoglobin, and cholesterol concentrations were not significantly altered compared with those of littermates placed on a chow diet. However, the serum ferritin level of animals in the iron-restricted group was 27% to 30% lower than that of the control group in either sex. Furthermore, the lipoproteins isolated from the iron-restricted group exhibited greater resistance to copper-induced oxidation. Histological examination revealed that atherosclerotic lesions developed in mice fed a low-iron diet were significantly smaller than those found in control littermates. Likewise, the iron deposition as well as tissue iron content was much less in aortic tissues of the iron-restricted animals. Circulating autoantibodies to oxidized LDL and immunostains for epitopes of malondialdehyde-modified LDL detected on lesions were also significantly lower in mice fed a low-iron diet. Conclusions—Iron deposition is closely associated with the progression of atherosclerosis in apoE-deficient mice. Restriction in dietary iron intake leads to significant inhibition of lesion formation in these animals. These results suggest that the beneficial effect of a low-iron diet may be mediated, at least in part, by the reduction of iron deposition as well as LDL oxidation in vascular lesions.
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Iron depletion by dietary or other means delays atherosclerosis.
“iron depletion by dietary or other means delays this [778-782].”
Iron depletion by dietary or other means delays the formation of atherosclerotic lesions.
“Iron depletion by dietary or other means delays the formation of such lesions”
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- Authors
- Lee, T.-S., Shiao, M.-S., Pan, C.-C., & Chau, L.-Y.
- Affiliations
- Taipei Veterans General Hospital (TW)
- Venue
- Circulation
- Published
- 1999-03-09
- Volume
- 99
- Issue
- 9
- Pages
- 1222-1229
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2001806476
- Cited by
- 179
- References
- 36
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 12 · 2014: 6 · 2013: 6 · 2012: 6
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council
- Academia Sinica
- Institute of Biomedical Sciences, Academia Sinica
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- iron deficiency, low-iron diet, atherosclerosis, ApoE-deficient mice, iron accumulation, serum ferritin, LDL oxidation, oxidized LDL autoantibodies, malondialdehyde-modified LDL, aortic lesions, copper-induced oxidation, dietary iron restriction
- MeSH terms
- Alkaline Phosphatase, Animals, Apolipoproteins E, Arteriosclerosis, Cholesterol, Diet, Disease Models, Animal, Female, Ferritins, Hemoglobins, Histocytochemistry, Immunohistochemistry, Iron, Lipoproteins, LDL, Male, Malondialdehyde, Mice, Inbred C57BL, Oxidation-Reduction, Mice, Knockout, Iron, Dietary, Mice
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