Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

Marie Laëtitia Thézénas, Bianca De Leo, Alexis Laux-Biehlmann, Cemsel Bafligil, Bernd Elger, Thomas Tapmeier, Karl Morten, Nilufer Rahmioglu, Stephanie G. Dakin, Philip Charles, Fernando Estrada Martinez, Graham Steers, Oliver M. Fischer, Joerg Mueller, Holger Hess-Stumpp, Andreas Steinmeyer, Sanjiv Manek, Krina T. Zondervan, Stephen Kennedy, Christian M. BeckerCatherine Shang, Thomas M. Zollner, Benedikt M. Kessler, Udo Oppermann

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Abstract

Endometriosis is a common gynaecological disease of women in reproductive age, and is thought to arise from retrograde menstruation and implantation of endometrial tissue, mostly into the peritoneal cavity. The condition is characterized by a chronic, unresolved inflammatory process thereby contributing to pain as cardinal symptom in endometriosis. Elevated reactive oxygen species (ROS) and oxidative stress have been postulated as factors in endometriosis pathogenesis. We here set out for a systematic study to identify novel mechanisms and pathways relating to oxidative stress in ectopic peritoneal lesions. Using combined proteomic and transcriptomic approaches, we identified novel targets including upregulated pro-oxidative enzymes, such as amine oxidase 3/vascular adhesion protein 1 (AOC3/VAP1) as well as downregulated protective factors, in particular alkenal reductase PTGR1 and methionine sulfoxide reductase. Consistent with an altered ROS landscape, we observed hemoglobin / iron overload, ROS production and lipid peroxidation in ectopic lesions. ROS-derived 4-hydroxy-2-nonenal induced interleukin IL-8 release from monocytes. Notably, AOC3 inhibitors provoked analgesic effects in inflammatory pain models in vivo, suggesting potential translational applicability.

Original languageEnglish
Article number1495
Number of pages11
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020
Externally publishedYes

Cite this

Thézénas, M. L., De Leo, B., Laux-Biehlmann, A., Bafligil, C., Elger, B., Tapmeier, T., Morten, K., Rahmioglu, N., Dakin, S. G., Charles, P., Martinez, F. E., Steers, G., Fischer, O. M., Mueller, J., Hess-Stumpp, H., Steinmeyer, A., Manek, S., Zondervan, K. T., Kennedy, S., ... Oppermann, U. (2020). Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions. Scientific Reports, 10(1), [1495]. https://doi.org/10.1038/s41598-020-58362-3