title: Macrophage phenotypes and their modulation in atherosclerosis.
abstract: 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.
authors.affiliation: Université Lille 2.
authors.forename: Federica
authors.initials: F
authors.lastname: De Paoli
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Giulia
authors.initials: G
authors.lastname: Chinetti-Gbaguidi
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D000090062:Kruppel-Like Factor 4; D008075:Lipoproteins, HDL / Q000276:immunology; D008264:Macrophages / Q000145:classification* / Q000276:immunology* / Q000473:pathology; D035683:MicroRNAs / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology; D013879:Thioredoxins / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D008075:Lipoproteins, HDL; D035683:MicroRNAs; C491203:TXN protein, human; D014157:Transcription Factors; D013879:Thioredoxins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases