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Myeloperoxidase promotes tube formation, triggers ERK1/2 and Akt pathways and is expressed endogenously in endothelial cells

Khalil, Alia, Medfai, Hayfa, Poelvoorde, Philippe, Kazan, Mohammad Fayyad, Delporte, Cedric, Van Antwerpen, Pierre, EL-Makhour, Yolla, Biston, Patrick, Delrée, Paul, Badran, Bassam, Vanhamme, Luc, Boudjeltia, Karim Zouaoui
Archives of biochemistry and biophysics 2018 v.654 pp. 55-69
RNA interference, angiogenesis, blood, blood vessels, catalytic activity, endothelial cells, endothelium, enzyme activity, exogenous sources, genes, mammals, mitogen-activated protein kinase, morphogenesis, myeloperoxidase, peroxidase, phagosomes, proteins, quantitative polymerase chain reaction, reverse transcriptase polymerase chain reaction, sequence analysis, signal transduction, transcriptome, vascular endothelial growth factors
Myeloperoxidase is a member of the mammalian peroxidase family, mainly expressed in the myeloblastic cell lineage. It is considered a major bactericidal agent as it is released in the phagosome where it catalyzes the formation of reactive oxygen species. It is also released in the extracellular spaces including blood where it is absorbed on (lipo)proteins and endothelial cell surface, interfering with endothelial function. We performed RNA sequencing on MPO-treated endothelial cells, analyzed their transcriptome and validated the profile of gene expression by individual qRT-PCR. Some of the induced genes could be grouped in several functional networks, including tubulogenesis, angiogenesis, and blood vessel morphogenesis and development as well as signal transduction pathways associated to these mechanisms. MPO treatment mimicked the effects of VEGF on several signal transduction pathways, such as Akt, ERK or FAK involved in angiogenesis. Accordingly MPO, independently of its enzymatic activity, stimulated tube formation by endothelial cells. RNA interference also pointed at a role of endogenous MPO in tubulogenesis and endothelium wound repair in vitro. These data suggest that MPO, whether from endogenous or exogenous sources, could play a role in angiogenesis and vascular repair in vivo.