Macrophages become foam cells following internalization of these oxidized LDLs through scavenger receptors. Calay and coworkers showed that myeloperoxidase-oxidized LDLs (MpOx-LDLs) activate different signaling cascades in macrophages compared to Ox-LDLs. However, most of the studies have focused on copper-oxidized LDLs (Ox-LDLs), while more relevant forms of oxidized LDLs have been neglected. They activate endothelial cells increasing their chemokine (e.g., MCP-1) and cytokine (e.g., IL-6) secretion, leading to the recruitment of monocytes, which will differentiate into macrophages within the intima. The oxidized lipoproteins are atherogenic. Local blood flow perturbations or injuries lead to an increased permeability of the endothelial layer, favoring lipoprotein infiltration in the intima, where they get oxidized. IntroductionĬardiovascular diseases, the major cause of deaths in western societies and throughout the world, are mainly due to atherosclerosis, a chronic inflammatory disease affecting mainly medium and large arteries (WHO, fact sheets of 2016). 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. These data were largely confirmed in murine bone marrow-derived macrophages. Noteworthy, MpOx-LDLs were the most efficient to accumulate lipids intracellularly in (un)polarized macrophages whatever the phenotype. MpOx-LDLs also modulate marker gene expression in polarized macrophages favoring notably anti-inflammatory Arg1 expression in M2 cells and also in the other phenotypes. Except for MRC1, which is induced only by Ox-LDLs, MpOx-LDLs induced an overexpression of most of the selected marker genes at the mRNA level. ![]() ![]() 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. The effects of physiologically relevant myeloperoxidase-oxidized LDLs on macrophage polarization or on polarized macrophages remain largely unknown. 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. Macrophages are prone to polarization and subsets of polarized macrophages have been described in atheromas. Macrophages and oxidized LDLs play a key role in atherogenesis but their heterogeneity has been neglected up to now.
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