0541966 - BFÚ 2022 RIV US eng J - Článek v odborném periodiku
Kolářová, Hana - Víteček, Jan - Černá, A. - Černík, Marek - Přibyl, J. - Skládal, P. - Potěšil, D. - Ihnatova, I. - Zdráhal, Z. - Hampl, A. - Klinke, A. - Kubala, Lukáš
Myeloperoxidase mediated alteration of endothelial function is dependent on its cationic charge.
Free Radical Biology and Medicine. Roč. 162, č. 2021 (2021). ISSN 0891-5849. E-ISSN 1873-4596
Institucionální podpora: RVO:68081707
Klíčová slova: junctions * Myeloperoxidase * Inflammation * Cardiovascular diseases * Glycocalyx * Endothelial cells
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 8.101, rok: 2021
Způsob publikování: Omezený přístup
Web výsledku:
https://www.sciencedirect.com/science/article/pii/S0891584920316063?via%3Dihub
DOI: https://doi.org/10.1016/j.freeradbiomed.2020.11.008

Endothelial cell (EC) glycocalyx (GLX) comprise a multicomponent layer of pmteoglycans and glycoproteins. Alteration of its integrity contributes to chronic vascular inflammation and leads to the development of cardiovascular diseases. Myeloperoxidase (MPO), a highly abundant enzyme released by polymorphonuclear neutrophils, binds to the GLX and deleteriously affects vascular EC functions. The focus of this study was to elucidate the mechanisms of MPO-mediated alteration of GLX molecules, and to unravel subsequent changes in endothelial integrity and function. MPO binding to GLX of human ECs and subsequent internalization was mediated by cell surface heparan sulfate chains. Moreover, interaction of MPO, which is carrying a cationic charge, with anionic glycosaminoglycans (GAGs) resulted in reduction of their relative charge. By means of micro-viscometry and atomic force microscopy, we disclosed that MPO can crosslink GAG chains. MPO-dependent modulation of GLX structure was further supported by alteration of wheat germ agglutinin staining. Increased expression of ICAM-1 documented endothelial cell activation by both catalytically active and also inactive MPO. Furthermore, MPO increased vascular permeability connected with reorganization of intracellular junctions, however, this was dependent on MPO's catalytic activity. Novel proteins interacting with MPO during transcytosis were identified by proteomic analysis. Altogether, these findings provide evidence that MPO through interaction with GAGs modulates overall charge of the GLX, causing modification of its structure and thus affecting EC function. Importantly, our results also suggest a number of proteins interacting with MPO that possess a variety of cellular localizations and functions.

Trvalý link: http://hdl.handle.net/11104/0319476