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Myeloperoxidase-oxidized LDLs: atherogenic particles with pro-inflammatory and pro-resolutive effect

par Van Antwerpen, Pierre
Référence 11th International Human Peroxidase Meeting (2-6 September 2019: Brno, Czec Republic)
Publication Non publié, 2019-09-02

Communication à un colloque

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Résumé :

Atherosclerosis is a chronic inflammatory syndrome where low-density lipoprotein (LDL) oxidation is an important process in its establishment and its development. An important contribution to the LDL oxidation mechanism comes from MPO. For twenty years, we have investigated the role of the MPO-oxidized LDLs (Mox-LDLs) in the context of atherogenesis. Indeed, MPO is adsorbed at the surface of LDL and adopts a conformational modification leading to an increase of its activity. As a consequence, LDLs are oxidized in the circulation or the sub-endothelial space and promote the production of IL-8 and TNF-alpha by endothelial cells and monocytes, respectively. In addition, they are present in atheroma plaques, delay fibrinolysis at the surface of endothelial cells and interfere with their mobility. When comparing copper-oxidized LDL (ox-LDLs) and Mox-LDL, we showed that Mox-LDLs are rapidly engulfed by macrophages compared to ox-LDLs and they promote the production of ROS. Interestingly, only Mox-LDLs induce the transcription of antioxidant factors such as heme oxygenase and gclm.These results prompted us to investigate further the properties of Mox-LDLs by analysing the effect of these particles on the inflammation resolution. Nowadays, inflammation resolution is considered as an active process where immune cells and anti-inflammatory factors, such as resolvins are involved. Resolvins, including resolvin D1 (RvD1), are derivate from oxidized-w3-lipids and reduce macrophage migration in the inflammatory tissue. In our experiments, we demonstrated that Mox-LDLs but not ox-LDLs induced a rapid production of RvD1 by endothelial cells and not by macrophages. More importantly, Mox-LDLs and Nat-LDLs act synergistically to promote this production. These results suggest that if Mox-LDLs were known to be pro-inflammatory and deleterious in the context of atherosclerosis, they are also able to induce a pro-resolution response by production of RvD1 by endothelial cells.