Macrophage heterogeneity in atherosclerotic plaques - PubMed (original) (raw)

Review

Macrophage heterogeneity in atherosclerotic plaques

Jason L Johnson et al. Curr Opin Lipidol. 2009 Oct.

Abstract

Purpose of review: The varied behaviour of macrophages and foam cells during atherosclerosis and its clinical sequelae prompt the question whether all these activities can be the property of a single cell population.

Recent findings: Subsets of monocytes with distinct patterns of surface markers and behaviours during inflammation have recently been characterized and shown to have complementary roles during progression of atherosclerosis. A variety of macrophage phenotypes derived from these monocyte subsets in response to mediators of innate and acquired immunity have also been found in plaques. Based on functional properties and genomic signatures, they may have different impacts on facets of plaque development, including fibrous cap and lipid core formation.

Summary: Monocyte and macrophage phenotypic diversity is important in atherogenesis. More work is needed to define consistent marker sets for the different foam cell phenotypes in experimental animals and humans. Cell tracking studies are needed to establish their relationship with monocyte subtypes. In addition, genetic and pharmacological manipulation of phenotypes will be useful to define their functions and exploit the resulting therapeutic potential.

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Figures

Figure 1

Figure 1. Origins of macrophage diversity

Recruitment of two different populations of monocytes and action of different mediators may lead to distinct macrophage phenotypes. Uptake of modified lipoproteins converts these to foam cells that may exert a variety of functions in plaque development. GM-CSF, granulocyte macrophage-colony stimulating factor; LPS, lipopolysaccharide; M-CSF, macrophage-colony stimulating factor.

Figure 2

Figure 2. A platform for studying function of foamy and non-foamy macrophages generated in vivo

Generation of nonfoamy and foam cell macrophages in subcutaneous sponges in rabbits yields pur preparations that can be subjected to analysis or gene transfer to determine functions that can be verified by immunocytochemistry in tissue sections. FCM, foam cell macrophage; ICC, immunocytochemistry; MMP, metalloproteinase; NFM, nonfoamy macrophage.

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References

    1. Hansson GK. Mechanisms of disease – inflammation, atherosclerosis, and coronary artery disease. New Engl J Med. 2005;352:1685–1695. - PubMed
    1. Nakashima Y, Fujii H, Sumiyoshi S, et al. Early human atherosclerosis: accumulation of lipid and proteoglycans in intimal thickenings followed by macrophage infiltration. Arterioscler Thromb Vasc Biol. 2007;27:1159–1165. - PubMed
    1. Swirski FK, Libby P, Aikawa E, et al. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest. 2007;117:195–205. - PMC - PubMed
    1. Tacke F, Alvarez D, Kaplan TJ, et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest. 2007;117:185–194. - PMC - PubMed
    1. Aikawa M, Rabkin E, Voglic SJ, et al. Lipid lowering promotes accumulation of mature smooth muscle cells expressing smooth muscle myosin heavy chain isoforms in rabbit atheroma. Circ Res. 1998;83:1015–1026. - PubMed

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