Macrophage plasticity in experimental atherosclerosis
Open accessAbstract
As in human disease, macrophages (MØ) are central players in the development and progression of experimental atherosclerosis. In this study we have evaluated the phenotype of MØ associated with progression of atherosclerosis in the apolipoprotein E (ApoE) knockout (KO) mouse model.We found that bone marrow-derived MØ submitted to M1 and M2 polarization specifically expressed arginase (Arg) II and Arg I, respectively. This distinct arginase expression was used to evaluate the frequency and distribution of M1 and M2 MØ in cross-sections of atherosclerotic plaques of ApoE KO mice. Early lesions were infiltrated by Arg I(+) (M2) MØ. This type of MØ favored the proliferation of smooth muscle cells, in vitro. Arg II(+) (M1) MØ appeared and prevailed in lesions of aged ApoE KO mice and lesion progression was correlated with the dominance of M1 over the M2 MØ phenotype. In order to address whether the M2->M1 switch could be due to a phenotypic switch of the infiltrated cells, we performed in vitro repolarization experiments. We found that fully polarized MØ retained their plasticity since they could revert their phenotype. The analysis of the distribution of Arg I- and Arg II-expressing MØ also argued against a recent recruitment of M1 MØ in the lesion. The combined data therefore suggest that the M2->M1 switch observed in vivo is due to a conversion of cells already present in the lesion. Our study suggests that interventional tools able to revert the MØ infiltrate towards the M2 phenotype may exert an atheroprotective action.
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Differentiation into M1 macrophages in the lesion becomes dominant in more advanced stages (>55 weeks).
“Differentiation into M1 macrophages in the lesion becomes dominant in more advanced stages (>55 weeks) ( 19 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [19]
The Results section (page not provided) compares 20- and 55-week-old ApoE KO mice, and the Discussion says M1 macrophages prevailed over M2 macrophages as lesions progressed. This supports M1 predominance in advanced lesions, but the paper reports mice at 55 weeks, not >55 weeks, and does not establish differentiation into M1 macrophages as the mechanism. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAt 20 weeks, plaque macrophages are mainly M2.
“We studied lesion development at an early stage (20 weeks), when plaque macrophages are mainly M2.”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [19]
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- Authors
- Khallou-Laschet, J., Varthaman, A., Fornasa, G., Compain, C., Gaston, A.-T., Clement, M., Dussiot, M., Levillain, O., Graff-Dubois, S., Nicoletti, A., & Caligiuri, G.
- Affiliations
- Inserm (FR)
- Lyon 1 Université (FR)
- Corresponding author
- Caligiuri, Giuseppina
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-01-25
- Volume
- 5
- Issue
- 1
- Pages
- e8852
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2810335
- OpenAlex
- W2035817205
- Cited by
- 517
- References
- 4
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 25 · 2023: 23 · 2022: 28 · 2021: 31 · 2020: 31 · 2019: 23 · 2018: 25 · 2017: 30 · 2016: 40 · 2015: 51 · 2014: 46 · 2013: 60 · 2012: 39
- FWCI
- 18.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Agence Nationale de la Recherche
- Fondation de France (2008-002724)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- macrophage plasticity, macrophage polarization, M1/M2 macrophages, arginase II, arginase-1, atherosclerosis, atherosclerotic plaque, ApoE-deficient mice, smooth muscle cell proliferation, macrophage repolarization, atheroprotection
- MeSH terms
- Animals, Apolipoproteins E, Disease Models, Animal, Macrophages, Muscle, Smooth, Vascular, Culture Media, Conditioned, Mice, Knockout, Cell Proliferation, Atherosclerosis, Mice
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