Cited by 391Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismPhagocytosis and Immune Regulation

Human Atherosclerotic Plaque Alternative Macrophages Display Low Cholesterol Handling but High Phagocytosis Because of Distinct Activities of the PPARγ and LXRα Pathways

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Chinetti-Gbaguidi, Giulia, Baron, Morgane, Bouhlel, Mohamed Amine, Vanhoutte, Jonathan, Copin, Corinne, Sebti, Yasmine, Derudas, Bruno, Mayi, Thérèse +6 more·2011·Circulation Research

Abstract

Rationale: A crucial step in atherogenesis is the infiltration of the subendothelial space of large arteries by monocytes where they differentiate into macrophages and transform into lipid-loaded foam cells. Macrophages are heterogeneous cells that adapt their response to environmental cytokines. Th1 cytokines promote monocyte differentiation into M1 macrophages, whereas Th2 cytokines trigger an “alternative” M2 phenotype. Objective: We previously reported the presence of CD68 + mannose receptor (MR) + M2 macrophages in human atherosclerotic plaques. However, the function of these plaque CD68 + MR + macrophages is still unknown. Methods and Results: Histological analysis revealed that CD68 + MR + macrophages locate far from the lipid core of the plaque and contain smaller lipid droplets compared to CD68 + MR − macrophages. Interleukin (IL)-4–polarized CD68 + MR + macrophages display a reduced capacity to handle and efflux cellular cholesterol because of low expression levels of the nuclear receptor liver x receptor (LXR)α and its target genes, ABCA1 and apolipoprotein E, attributable to the high 15-lipoxygenase activity in CD68 + MR + macrophages. By contrast, CD68 + MR + macrophages highly express opsonins and receptors involved in phagocytosis, resulting in high phagocytic activity. In M2 macrophages, peroxisome proliferator-activated receptor (PPAR)γ activation enhances the phagocytic but not the cholesterol trafficking pathways. Conclusions: These data identify a distinct macrophage subpopulation with a low susceptibility to become foam cells but high phagocytic activity resulting from different regulatory activities of the PPARγ-LXRα pathways.

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Crossref · 10.1161/circresaha.110.233775

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Authors
Chinetti-Gbaguidi, G., Baron, M., Bouhlel, M. A., Vanhoutte, J., Copin, C., Sebti, Y., Derudas, B., Mayi, T., Bories, G., Tailleux, A., Haulon, S., Zawadzki, C., Jude, B., & Staels, B.
Affiliations
  • From Univ Lille Nord de France (G.C.-G., M.B., M.A.B., J.V., C.C., Y.S., B.D., T.M., G.B., A.T., C.Z., B.J., B.S.), F-59000, Lille; Inserm (G.C.-G., M.B., M.A.B., J.V., C.C., Y.S., B.D., T.M., G.B., A.T., B.S.), U1011, F-59000, Lille; UDSL (G.C.-G., M.B., M.A.B., J.V., C.C., Y.S., B.D., T.M., G.B., A.T., C.Z., B.J., B.S.), F-59000, Lille, France; Institut Pasteur de Lille (G.C.-G., M.B., M.A.B., J.V., C.C., Y.S., B.D., T.M., G.B., A.T., B.S.), F-59019, Lille; and EA2693 and Centre Hospitalier...
  • Inserm (FR)
Venue
Circulation Research
Published
2011-04-15
Volume
108
Issue
8
Pages
985-995
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
OpenAlex
W2129909114
Cited by
387
References
43
Citations by year
2026: 14 · 2025: 19 · 2024: 25 · 2023: 22 · 2022: 34 · 2021: 17 · 2020: 21 · 2019: 30 · 2018: 26 · 2017: 30 · 2016: 21 · 2015: 28 · 2014: 25 · 2013: 29 · 2012: 31
FWCI
14.18
Type
journal article
Language
en
Open access
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, other-oa)
  • LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords
M2 macrophages, CD206, CD68, phagocytosis, cholesterol efflux, ABCA1, apolipoprotein E, liver X receptor alpha, PPARγ, 15-lipoxygenase, foam cells, macrophage heterogeneity, opsonins
MeSH terms
Liver X Receptors, Cell Differentiation, Cells, Cultured, Cholesterol, Humans, Leukocytes, Mononuclear, Macrophages, Phagocytosis, Genetic Predisposition to Disease, PPAR gamma, Orphan Nuclear Receptors, Plaque, Atherosclerotic

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