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  • Review Article
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Macrophage subsets in atherosclerosis

Nature Reviews Cardiology volume 12, pages 10–17 (2015)Cite this article

Subjects

Key Points

  • Only M1 proinflammatory and M2 anti-inflammatory macrophages have been described in vitro—however, a wide spectrum of intermediate phenotypes has been identified in in vivo studies

  • Various stimuli (cytokines, lipids and their derivatives, senescent cells, iron) can influence macrophage phenotypes in atherosclerotic lesions

  • Macrophages with different functional phenotypes are likely to perform different roles in the development of atherosclerosis

  • M1 macrophages are associated with symptomatic and unstable plaques, whereas M2 macrophages are particularly abundant in stable zones of the plaque and asymptomatic lesions

  • Modulation of macrophage phenotypes might be a novel strategy for the pharmacological treatment of atherosclerosis

Abstract

Macrophage accumulation within the vascular wall is a hallmark of atherosclerosis. In atherosclerotic lesions, macrophages respond to various environmental stimuli, such as modified lipids, cytokines, and senescent erythrocytes, which can modify their functional phenotypes. The results of studies on human atherosclerotic plaques demonstrate that the relative proportions of macrophage subsets within a plaque might be a better indicator of plaque phenotype and stability than the total number of macrophages. Understanding the function of specific macrophage subsets and their contribution to the composition and growth of atherosclerotic plaques would aid the identification of novel strategies to delay or halt the development of the disease and its associated pathophysiological consequences. However, most studies aimed at characterizing the phenotypes of human macrophages are performed in vitro and, therefore, their functional relevance to human pathology remains uncertain. In this Review, the diverse range of macrophage phenotypes in atherosclerotic lesions and their potential roles in both plaque progression and stability are discussed, with an emphasis on human pathology.

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Figure 1: Potential role of M2 macrophages in efferocytosis within atherosclerotic plaques.
Figure 2: Main macrophage subtypes found in atherosclerotic lesions.
Figure 3: Localization of macrophage subsets in human atherosclerotic lesions.

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Acknowledgements

The authors acknowledge grants from the Fondation de France (G.C.-G.), the Fondation pour la Recherche Médicale (G.C.-G.), and the Transatlantic Leducq HDL Network (B.S.). B.S. is a member of the Institut Universitaire de France.

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  1. INSERM U1011, Institut Pasteur de Lille, 1, Rue du Professeur Calmette, BP 245, Lille, 59019, France

    Giulia Chinetti-Gbaguidi, Sophie Colin & Bart Staels

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  1. Giulia Chinetti-Gbaguidi
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G.C.-G. and S.C. researched data for the article. S.C. and B.S. substantially contributed to the discussion of content. G.C.-G. wrote the manuscript. B.S. reviewed and edited the manuscript before submission.

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Correspondence to Bart Staels.

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Chinetti-Gbaguidi, G., Colin, S. & Staels, B. Macrophage subsets in atherosclerosis. Nat Rev Cardiol 12, 10–17 (2015). https://doi.org/10.1038/nrcardio.2014.173

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