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Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARγ and LXRα pathways.: Atherosclerotic plaque alternative macrophages
- Source :
- Circulation Research, Circulation Research, American Heart Association, 2011, 108 (8), pp.985-95. ⟨10.1161/CIRCRESAHA.110.233775⟩
- Publication Year :
- 2011
- Publisher :
- HAL CCSD, 2011.
-
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.
- Subjects :
- Apolipoprotein E
MESH: Cell Differentiation
Physiology
nuclear receptors
030204 cardiovascular system & hematology
Article
03 medical and health sciences
0302 clinical medicine
MESH: Cholesterol
Phagocytosis
Lipid droplet
Humans
Genetic Predisposition to Disease
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
MESH: Plaque, Atherosclerotic
Liver X receptor
MESH: Phagocytosis
Cells, Cultured
030304 developmental biology
Liver X Receptors
0303 health sciences
MESH: Humans
biology
CD68
MESH: Genetic Predisposition to Disease
Interleukin
cholesterol
MESH: Macrophages
Cell Differentiation
Orphan Nuclear Receptors
Atherosclerosis
Plaque, Atherosclerotic
Cell biology
macrophages
PPAR gamma
MESH: Leukocytes, Mononuclear
Biochemistry
MESH: Orphan Nuclear Receptors
MESH: PPAR gamma
Monocyte differentiation
ABCA1
biology.protein
Leukocytes, Mononuclear
Cardiology and Cardiovascular Medicine
Mannose receptor
MESH: Cells, Cultured
Subjects
Details
- Language :
- English
- ISSN :
- 00097330 and 15244571
- Database :
- OpenAIRE
- Journal :
- Circulation Research, Circulation Research, American Heart Association, 2011, 108 (8), pp.985-95. ⟨10.1161/CIRCRESAHA.110.233775⟩
- Accession number :
- edsair.doi.dedup.....e7706ab2bbf01d5c21de1399ec3ca223