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Remodeling of the endothelial cell transcriptional program via paracrine and DNA-binding activities of MPO

Abstract: 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.

 Autoría: Zheng R., Moynahan K., Georgomanolis T., Pavlenko E., Geissen S., Mizi A., Grimm S., Nemade H., Rehimi R., Bastigkeit J., Lackmann J.W., Adam M., Rada-Iglesias A., Nuernberg P., Klinke A., Poepsel S., Baldus S., Papantonis A., Kargapolova Y.,

 Fuente: iScience, 2024, 27(2), 108898

Editorial: Elsevier

 Año de publicación: 2024

Nº de páginas: 20

Tipo de publicación: Artículo de Revista

 DOI: 10.1016/j.isci.2024.108898

ISSN: 2589-0042

Url de la publicación: https://doi.org/10.1016/j.isci.2024.108898

Autoría

ZHENG, RUIYUAN

MOYNAHAN, KYLE

GEORGOMANOLIS, THEODOROS

PAVLENKO, EGOR

GEISSEN, SIMON

MIZI, ATHANASIA

GRIMM, SIMON

NEMADE, HARSHAL

REHIMI, RIZWAN

BASTIGKEIT, JIL

LACKMANN, JAN-WILM

ADAM, MATTI

NUERNBERG, PETER

KLINKE, ANNA

POEPSEL, SIMON

BALDUS, STEPHAN

PAPANTONIS, ARGYRIS

KARGAPOLOVA, YULIA