(Circulation. 1999;99:1222-1229.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Iron-Deficient Diet Reduces Atherosclerotic Lesions in ApoE-Deficient Mice
From the Division of Cardiovascular Research, Institute of Biomedical Sciences, Academia Sinica (T.-S.L., C.-C.P., L.-Y.C.), and the Lipid Metabolism Laboratory, Department of Medical Research and Education, Veterans General Hospital (M.-S.S.), Taipei, Taiwan, ROC.
Correspondence to Lee-Young Chau, PhD, Division of Cardiovascular Research, Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, 11529, Taiwan, ROC. E-mail lyc{at}mail.ibms.sinica.edu.tw
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.
Key Words: atherosclerosis • iron • lipoproteins • oxygen
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