@article{10902/31992,
year = {2024},
url = {https://hdl.handle.net/10902/31992},
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.},
publisher = {Elsevier},
publisher = {iScience, 2024, 27(2), 108898},
title = {Remodeling of the endothelial cell transcriptional program via paracrine and DNA-binding activities of MPO},
author = {Zheng, Ruiyuan and Moynahan, Kyle and Georgomanolis, Theodoros and Pavlenko, Egor and Geissen, Simon and Mizi, Athanasia and Grimm, Simon and Nemade, Harshal and Rehimi, Rizwan and Bastigkeit, Jil and Lackmann, Jan-Wilm and Adam, Matti and Rada Iglesias, Álvaro and Nuernberg, Peter and Klinke, Anna and Poepsel, Simon and Baldus, Stephan and Papantonis, Argyris and Kargapolova, Yulia},
}