Macrophage Phenotypes and Their Modulation in Atherosclerosis

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  • De Paoli Federica
    Université Lille 2 Inserm Lille Institut Pasteur de Lille European Genomic Institute for Diabetes (EGID)
  • Staels Bart
    Université Lille 2 Inserm Lille Institut Pasteur de Lille European Genomic Institute for Diabetes (EGID)
  • Chinetti-Gbaguidi Giulia
    Université Lille 2 Inserm Lille Institut Pasteur de Lille European Genomic Institute for Diabetes (EGID)

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Atherosclerosis is the result of a chronic inflammatory response in the arterial wall related to uptake of low-density lipoprotein by macrophages and their subsequent transformation in foam cells. Monocyte-derived macrophages are the principal mediators of tissue homeostasis and repair, response to pathogens and inflammation. However, macrophages are a homogeneous cell population presenting a continuum phenotypic spectrum with, at the extremes, the classically Th-1 polarized M1 and alternatively Th-2 polarized M2 macrophage phenotypes, which have been well described. Moreover, M2 macrophages also present several subtypes often termed M2a, b, c and d, each of them expressing specific markers and exhibiting specialized properties. Macrophage plasticity is mirrored also in the atherosclerotic lesions, where different stimuli can influence the phenotype giving rise to a complex system of subpopulations, such as Mox, Mhem, M(Hb) and M4 macrophages. An abundant literature has described the potential modulators of the reciprocal skewing between pro-inflammatory M1 and anti-inflammatory M2 macrophages including lesion stage and localization, miRNA, transcription factors such as PPARγ, KLF4 and NR4A family members, high-density lipoproteins and plaque lipid content, pathways such as the rapamycin-mTOR1 pathway, molecules such as thioredoxin-1, infection by helminths and irradiation. We hope to provide an overview of the macrophage phenotype complexity in cardiovascular diseases, particularly atherosclerosis. (Circ J 2014; 78: 1775–1781)

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  • Circulation Journal

    Circulation Journal 78 (8), 1775-1781, 2014

    一般社団法人 日本循環器学会

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