Title

Overexpression Of Transferrin Receptor And Ferritin Related To Clinical Symptoms And Destabilization Of Human Carotid Plaques

Keywords

Apoptosis; Atherosclerosis; Iron metabolism; Lysosomes; Macrophages; Plaque rupture

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 highly 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 I caused by atheroma-relevant lipids in atherogenesis. Copyright © 2008 by the Society for Experimental Biology and Medicine.

Publication Date

7-1-2008

Publication Title

Experimental Biology and Medicine

Volume

233

Issue

7

Number of Pages

818-826

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.3181/0711-RM-320

Socpus ID

47749122193 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/47749122193

This document is currently not available here.

Share

COinS