Universität zu Köln

Zheng, Ruiyuan ORCID: 0000-0002-7594-3869, Moynahan, Kyle, Georgomanolis, Theodoros ORCID: 0000-0002-4066-9257, Pavlenko, Egor ORCID: 0000-0003-0293-052X, Geissen, Simon ORCID: 0000-0002-7835-4111, Mizi, Athanasia, Grimm, Simon ORCID: 0000-0002-0786-2207, Nemade, Harshal ORCID: 0000-0002-2704-181X, Rehimi, Rizwan, Bastigkeit, Jil ORCID: 0000-0001-9148-4044, Lackmann, Jan-Wilm ORCID: 0000-0001-8182-8034, Adam, Matti ORCID: 0000-0002-6990-8135, Rada-Iglesias, Alvaro, Nuernberg, Peter ORCID: 0009-0009-8276-7910, Klinke, Anna, Poepsel, Simon ORCID: 0000-0002-8304-4062, Baldus, Stephan ORCID: 0000-0001-8259-1737, Papantonis, Argyris and Kargapolova, Yulia ORCID: 0000-0001-7541-5778 (2024). Remodeling of the endothelial cell transcriptional program via paracrine and DNA-binding activities of MPO. iScience, 27 (2). pp. 1-20. Elsevier. ISSN 2589-0042

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Abstract

[Artikel-Nr.: 108898] Myeloperoxidase (MPO) is an enzyme that functions in host defense. MPO is released into the vascular lumen by neutrophils during inflammation and may adhere and subsequently penetrate endothelial cells (ECs) coating vascular walls. We show that MPO enters the nucleus of ECs and binds chromatin independently of its enzymatic activity. MPO drives chromatin decondensation at its binding sites and enhances condensation at neighboring regions. It binds loci relevant for endothelial-to-mesenchymal transition (EndMT) and affects the migratory potential of ECs. Finally, MPO interacts with the RNA-binding factor ILF3 thereby affecting its relative abundance between cytoplasm and nucleus. This interaction leads to change in stability of ILF3-bound transcripts. MPO-knockout mice exhibit reduced number of ECs at scar sites following myocardial infarction, indicating reduced neovascularization. In summary, we describe a non-enzymatic role for MPO in coordinating EndMT and controlling the fate of endothelial cells through direct chromatin binding and association with co-factors.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Zheng, Ruiyuan UNSPECIFIED https://orcid.org/0000-0002-7594-3869 UNSPECIFIED Moynahan, Kyle UNSPECIFIED UNSPECIFIED UNSPECIFIED Georgomanolis, Theodoros UNSPECIFIED https://orcid.org/0000-0002-4066-9257 UNSPECIFIED Pavlenko, Egor UNSPECIFIED https://orcid.org/0000-0003-0293-052X UNSPECIFIED Geissen, Simon UNSPECIFIED https://orcid.org/0000-0002-7835-4111 UNSPECIFIED Mizi, Athanasia UNSPECIFIED UNSPECIFIED UNSPECIFIED Grimm, Simon UNSPECIFIED https://orcid.org/0000-0002-0786-2207 UNSPECIFIED Nemade, Harshal UNSPECIFIED https://orcid.org/0000-0002-2704-181X UNSPECIFIED Rehimi, Rizwan UNSPECIFIED UNSPECIFIED UNSPECIFIED Bastigkeit, Jil UNSPECIFIED https://orcid.org/0000-0001-9148-4044 UNSPECIFIED Lackmann, Jan-Wilm UNSPECIFIED https://orcid.org/0000-0001-8182-8034 UNSPECIFIED Adam, Matti UNSPECIFIED https://orcid.org/0000-0002-6990-8135 UNSPECIFIED Rada-Iglesias, Alvaro UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED https://orcid.org/0009-0009-8276-7910 UNSPECIFIED Klinke, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Poepsel, Simon UNSPECIFIED https://orcid.org/0000-0002-8304-4062 UNSPECIFIED Baldus, Stephan UNSPECIFIED https://orcid.org/0000-0001-8259-1737 UNSPECIFIED Papantonis, Argyris UNSPECIFIED UNSPECIFIED UNSPECIFIED Kargapolova, Yulia UNSPECIFIED https://orcid.org/0000-0001-7541-5778 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-814008
Identification Number:	10.1016/j.isci.2024.108898
Journal or Publication Title:	iScience
Volume:	27
Number:	2
Page Range:	pp. 1-20
Number of Pages:	20
Date:	16 February 2024
Publisher:	Elsevier
ISSN:	2589-0042
Language:	English
Faculty:	Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Cologne Center for Genomics Faculty of Medicine > Innere Medizin > Klinik III für Innere Medizin - Kardiologie, Pneumologie, Angiologie und internistische Intensivmedizin Zentrum für Molekulare Medizin
Subjects:	Life sciences Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81400