Title

Overexpression of transferrin receptor and ferritin related to clinical symptoms and destabilization of human carotid plaques

Authors

Authors

W. Li; L. H. Xu; C. Forssell; J. L. Sullivan;X. M. Yuan

Comments

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Abbreviated Journal Title

Exp. Biol. Med.

Keywords

atherosclerosis; apoptosis; iron metabolism; lysosomes; macrophages; plaque rupture; HUMAN ATHEROSCLEROTIC PLAQUES; LOW-DENSITY-LIPOPROTEIN; HUMAN ATHEROMA; IRON HYPOTHESIS; DEFICIENT MICE; MACROPHAGE; EXPRESSION; RELEASE; CANCER; DAMAGE; Medicine, Research & Experimental

Abstract

Accumulation of tissue iron has been implicated in development of atherosclerotic lesions mainly because of increased iron-catalyzed oxidative injury. However, it remains unknown whether cellular iron import and storage in human atheroma are related to human atheroma development. We found that transferrin receptor 1 (TfR1), a major iron importer, is highy expressed in foamy macrophages and some smooth muscle cells in intimal lesions of human carotid atheroma, mainly in cytoplasmic accumulation patterns. In 52 human carotid atherosclerotic lesions, TfR1 expression was positively correlated with macrophage infiltration, ectopic lysosomal cathepsin L, and ferritin expression. Highly expressed TfR1 and ferritin in CD68-positive macrophages; were significantly associated with development and severity of human carotid plaques, smoking, and patient's symptoms. The findings suggest that pathologic macrophage iron metabolism may contribute to vulnerability of human atheroma, established risk factors, and their clinical symptoms. The cytoplasmic overexpression of TfR1 may be the result of lysosomal dysfunction and ectopic accumulation of lysosomal cathepsin L caused by atheroma-relevant lipids in atherogenesis.

Journal Title

Experimental Biology and Medicine

Volume

233

Issue/Number

7

Publication Date

1-1-2008

Document Type

Article

Language

English

First Page

818

Last Page

826

WOS Identifier

WOS:000257154500005

ISSN

1535-3702

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