The role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis

Iron is an essential mineral needed for normal physiologic processes. While its function in oxygen transport and other important physiologic processes is well known, less is understood about its role in inflammatory diseases such as atherosclerosis. Existing paradigms suggest iron as a driver of ath...

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Main Authors:	Habib, Anwer, Finn, Aloke V.
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145350/

id	pubmed-4145350
recordtype	oai_dc
spelling	pubmed-41453502014-09-12 The role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis Habib, Anwer Finn, Aloke V. Pharmacology Iron is an essential mineral needed for normal physiologic processes. While its function in oxygen transport and other important physiologic processes is well known, less is understood about its role in inflammatory diseases such as atherosclerosis. Existing paradigms suggest iron as a driver of atherosclerosis through its actions as a pro-oxidant capable of causing lipid oxidation and tissue damage. Recently we and others have identified hemoglobin (Hb) derived iron as an important factor in determining macrophage differentiation and function in areas of intraplaque hemorrhage within human atherosclerosis. Hb associated macrophages, M(Hb), are distinct from traditional macrophage foam cells because they do not contain large amounts of lipid or inflammatory cytokines, are characterized by high levels of expression of mannose receptor (CD206) and CD163 in addition to producing anti-inflammatory cytokines such as IL-10. Despite the well-known role of iron as an catalyst capable of producing lipid peroxidation through generation of reactive oxygen species (ROS) such as hydroxyl radical, we and others have shown that macrophages in areas of intraplaque hemorrhage demonstrate reduced intracellular iron and ROS which triggers production of anti-inflammatory cytokines as well as genes involved in cholesterol eﬄux. These data suggest that manipulation of macrophage iron itself may be a promising pharmacologic target for atherosclerosis prevention through its effects on macrophage inflammation and lipid metabolism. In this review we will summarize the current understanding of iron as it relates to plaque inflammation and discuss how further exploration of this subject may lead to new therapies for atherosclerosis. Frontiers Media S.A. 2014-08-27 /pmc/articles/PMC4145350/ /pubmed/25221512 http://dx.doi.org/10.3389/fphar.2014.00195 Text en Copyright © 2014 Habib and Finn. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Habib, Anwer Finn, Aloke V.
spellingShingle	Habib, Anwer Finn, Aloke V. The role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis
author_facet	Habib, Anwer Finn, Aloke V.
author_sort	Habib, Anwer
title	The role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis
title_short	The role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis
title_full	The role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis
title_fullStr	The role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis
title_full_unstemmed	The role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis
title_sort	role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis
description	Iron is an essential mineral needed for normal physiologic processes. While its function in oxygen transport and other important physiologic processes is well known, less is understood about its role in inflammatory diseases such as atherosclerosis. Existing paradigms suggest iron as a driver of atherosclerosis through its actions as a pro-oxidant capable of causing lipid oxidation and tissue damage. Recently we and others have identified hemoglobin (Hb) derived iron as an important factor in determining macrophage differentiation and function in areas of intraplaque hemorrhage within human atherosclerosis. Hb associated macrophages, M(Hb), are distinct from traditional macrophage foam cells because they do not contain large amounts of lipid or inflammatory cytokines, are characterized by high levels of expression of mannose receptor (CD206) and CD163 in addition to producing anti-inflammatory cytokines such as IL-10. Despite the well-known role of iron as an catalyst capable of producing lipid peroxidation through generation of reactive oxygen species (ROS) such as hydroxyl radical, we and others have shown that macrophages in areas of intraplaque hemorrhage demonstrate reduced intracellular iron and ROS which triggers production of anti-inflammatory cytokines as well as genes involved in cholesterol eﬄux. These data suggest that manipulation of macrophage iron itself may be a promising pharmacologic target for atherosclerosis prevention through its effects on macrophage inflammation and lipid metabolism. In this review we will summarize the current understanding of iron as it relates to plaque inflammation and discuss how further exploration of this subject may lead to new therapies for atherosclerosis.
publisher	Frontiers Media S.A.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145350/
_version_	1613127926797041664

The role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis

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