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Biochim Biophys Acta. 2009 Jul;1790(7):718-23. doi: 10.1016/j.bbagen.2008.06.005. Epub 2008 Jun 19.

Iron in arterial plaque: modifiable risk factor for atherosclerosis.

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  • 1Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, Florida, USA. jlsullivan3@gmail.com

Abstract

It has been proposed that iron depletion protects against cardiovascular disease. There is increasing evidence that one mechanism for this protection may involve a reduction in iron levels within atherosclerotic plaque. Large increases in iron concentration are seen in human atherosclerotic lesions in comparison to levels in healthy arterial tissue. In animal models, depletion of lesion iron levels in vivo by phlebotomy, systemic iron chelation treatment or dietary iron restriction reduces lesion size and/or increases plaque stability. A number of factors associated with increased arterial disease or increased cardiovascular events is also associated with increased plaque iron. In rats, infusion of angiotensin II increases ferritin levels and arterial thickness which are reversed by treatment with the iron chelator deferoxamine. In humans, a polymorphism for haptoglobin associated with increased cardiovascular disease is also characterized by increased lesional iron. Heme oxygenase 1 (HO1) is an important component of the system for mobilization of iron from macrophages. Human HO1 promoter polymorphisms causing weaker upregulation of the enzyme are associated with increased cardiovascular disease and increased serum ferritin. Increased cardiovascular disease associated with inflammation may be in part caused by elevated hepcidin levels that promote retention of iron within plaque macrophages. Defective retention of iron within arterial macrophages in genetic hemochromatosis may explain why there is little evidence of increased atherosclerosis in this disorder despite systemic iron overload. The reviewed findings support the concept that arterial plaque iron is a modifiable risk factor for atherogenesis.

PMID:
18619522
DOI:
10.1016/j.bbagen.2008.06.005
[PubMed - indexed for MEDLINE]
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