Title

Iron in arterial plaque: A modifiable risk factor for atherosclerosis

Authors

Authors

J. L. Sullivan

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

Biochim. Biophys. Acta-Gen. Subj.

Keywords

Iron; Atherosclerosis; Macrophage; Ferritin; Hemochromatosis; Hepcidin; Haptoglobin; Heme oxygenase; Angiotensin; Inflammation; Interleukin-6; ISCHEMIC-HEART-DISEASE; HEME OXYGENASE-1 EXPRESSION; CHRONIC; HEPATITIS-C; LUNG INJURY; STORED IRON; DEFICIENT DIET; HEREDITARY; HEMOCHROMATOSIS; CARDIOVASCULAR OUTCOMES; NUCLEAR MICROSCOPY; ENDOTHELIAL-CELLS; Biochemistry & Molecular Biology; Biophysics

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 11 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. (C) 2008 Elsevier B.V. All rights reserved.

Journal Title

Biochimica Et Biophysica Acta-General Subjects

Volume

1790

Issue/Number

7

Publication Date

1-1-2009

Document Type

Review

Language

English

First Page

718

Last Page

723

WOS Identifier

WOS:000267467100016

ISSN

0304-4165

Share

COinS