title: Myeloperoxidase-Oxidized LDLs Enhance an Anti-Inflammatory M2 and Antioxidant Phenotype in Murine Macrophages.
abstract: Macrophages and oxidized LDLs play a key role in atherogenesis but their heterogeneity has been neglected up to now. Macrophages are prone to polarization and subsets of polarized macrophages have been described in atheromas. LDLs can be oxidized not only chemically by copper (Ox-LDLs) but also enzymatically by myeloperoxidase (MpOx-LDLs) resulting in oxidized LDLs poor in lipid peroxides. The effects of physiologically relevant myeloperoxidase-oxidized LDLs on macrophage polarization or on polarized macrophages remain largely unknown. In this study, the effects of LDLs on macrophage polarization were investigated by monitoring the expression of M1 and M2 genes following stimulation with native LDLs, Ox-LDLs, or MpOx-LDLs in RAW 264.7 cells. Except forMRC1, which is induced only by Ox-LDLs, MpOx-LDLs induced an overexpression of most of the selected marker genes at the mRNA level. MpOx-LDLs also modulate marker gene expression in polarized macrophages favoring notably anti-inflammatoryArg1expression in M2 cells and also in the other phenotypes. Noteworthy, MpOx-LDLs were the most efficient to accumulate lipids intracellularly in (un)polarized macrophages whatever the phenotype. These data were largely confirmed in murine bone marrow-derived macrophages. Our data suggest that MpOx-LDLs were the most efficient to accumulate within cells and to enhance an anti-inflammatory and antioxidant phenotype in M2 cells and also in the other macrophage phenotypes.
authors.affiliation: URBC-Narilis, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Valérie
authors.identifier: 0000-0003-3262-3379
authors.initials: V
authors.lastname: Pireaux
authors.affiliation: URBC-Narilis, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Aude
authors.initials: A
authors.lastname: Sauvage
authors.affiliation: UMBD, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Benoît
authors.identifier: 0000-0002-8713-6319
authors.initials: B
authors.lastname: Bihin
authors.affiliation: URBC-Narilis, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: Van Steenbrugge
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), Université Libre de Bruxelles, CHU-Charleroi, ISPPC Hôpital Vésale, Montigny-Le-Tilleul, Belgium.
authors.forename: Alexandre
authors.identifier: 0000-0002-0228-9237
authors.initials: A
authors.lastname: Rousseau
authors.affiliation: Therapeutic Chemistry, ULB (Campus de la Plaine) CP205/05, boulevard du Triomphe, Brussels, Belgium.
authors.forename: Pierre
authors.identifier: 0000-0002-4934-8863
authors.initials: P
authors.lastname: Van Antwerpen
authors.affiliation: Laboratory of Experimental Medicine (ULB 222 Unit), Université Libre de Bruxelles, CHU-Charleroi, ISPPC Hôpital Vésale, Montigny-Le-Tilleul, Belgium.
authors.forename: Karim
authors.identifier: 0000-0002-3163-4212
authors.initials: K
authors.lastname: Zouaoui Boudjeltia
authors.affiliation: URBC-Narilis, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Martine
authors.identifier: 0000-0003-0954-1877
authors.initials: M
authors.lastname: Raes