[HTML][HTML] Macrophage plasticity in experimental atherosclerosis

J Khallou-Laschet, A Varthaman, G Fornasa… - PloS one, 2010 - journals.plos.org
J Khallou-Laschet, A Varthaman, G Fornasa, C Compain, AT Gaston, M Clement, M Dussiot…
PloS one, 2010journals.plos.org
As in human disease, macrophages (MŲ) are central players in the development and
progression of experimental atherosclerosis. In this study we have evaluated the phenotype
of MŲ associated with progression of atherosclerosis in the apolipoprotein E (ApoE)
knockout (KO) mouse model. We found that bone marrow-derived MŲ 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 MŲ …
As in human disease, macrophages (MŲ) are central players in the development and progression of experimental atherosclerosis. In this study we have evaluated the phenotype of MŲ associated with progression of atherosclerosis in the apolipoprotein E (ApoE) knockout (KO) mouse model.
We found that bone marrow-derived MŲ 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 MŲ in cross-sections of atherosclerotic plaques of ApoE KO mice. Early lesions were infiltrated by Arg I+ (M2) MŲ. This type of MŲ favored the proliferation of smooth muscle cells, in vitro. Arg II+ (M1) MŲ appeared and prevailed in lesions of aged ApoE KO mice and lesion progression was correlated with the dominance of M1 over the M2 MŲ 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 MŲ retained their plasticity since they could revert their phenotype. The analysis of the distribution of Arg I- and Arg II-expressing MŲ also argued against a recent recruitment of M1 MŲ 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 MŲ infiltrate towards the M2 phenotype may exert an atheroprotective action.
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