T S Lee1, M S Shiao, C C Pan, L Y Chau. 1. Division of Cardiovascular Research, Institute of Biomedical Sciences, Academia Sinica Laboratory, Taipei, Taiwan.
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.
BACKGROUND:Iron deposition is evident in humanatherosclerotic 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.
Authors: Subha V Raman; Travis P Sharkey-Toppen; Tam Tran; Jim X Liu; Beth McCarthy; Xin He; Suzanne Smart; Martha Gulati; Randell Wexler; Orlando P Simonetti; Rebecca D Jackson Journal: Atherosclerosis Date: 2015-03-20 Impact factor: 5.162
Authors: Vaijinath S Kamanna; Shobha H Ganji; Stanislav Shelkovnikov; Keith Norris; Nosratola D Vaziri Journal: Am J Nephrol Date: 2011-12-29 Impact factor: 3.754
Authors: Rajeev Malhotra; Florian Wunderer; Hanna J Barnes; Aranya Bagchi; Mary D Buswell; Caitlin D O'Rourke; Charles L Slocum; Clara D Ledsky; Kathryn M Peneyra; Haakon Sigurslid; Benjamin Corman; Kimberly B Johansson; David K Rhee; Kenneth D Bloch; Donald B Bloch Journal: Arterioscler Thromb Vasc Biol Date: 2019-02 Impact factor: 8.311
Authors: Florian Wunderer; Lisa Traeger; Haakon H Sigurslid; Patrick Meybohm; Donald B Bloch; Rajeev Malhotra Journal: Pharmacol Res Date: 2020-01-25 Impact factor: 7.658
Authors: Aron M Troen; Esther Lutgens; Donald E Smith; Irwin H Rosenberg; Jacob Selhub Journal: Proc Natl Acad Sci U S A Date: 2003-12-01 Impact factor: 11.205