Myeloperoxidase mediated alteration of endothelial function is dependent on its cationic charge

Kolářová, Hana; Víteček, Jan; Černá, A.; Černík, Marek; Přibyl, J.; Skládal, P.; Potěšil, D.; Ihnatova, I.; Zdráhal, Z.; Hampl, A.; Klinke, A.; Kubala, Lukáš

doi:https://dx.doi.org/10.1016/j.freeradbiomed.2020.11.008

Number of the records: 1

Myeloperoxidase mediated alteration of endothelial function is dependent on its cationic charge

1.

SYSNO ASEP	0541966
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Myeloperoxidase mediated alteration of endothelial function is dependent on its cationic charge
Author(s)	Kolářová, Hana (BFU-R)_RID Víteček, Jan (BFU-R)_{RID, ORCID} Černá, A. (CZ) Černík, Marek (BFU-R)_ORCID Přibyl, J. (CZ) Skládal, P. (CZ) Potěšil, D. (CZ) Ihnatova, I. (CZ) Zdráhal, Z. (CZ) Hampl, A. (CZ) Klinke, A. (DE) Kubala, Lukáš (BFU-R)_{RID, ORCID}
Number of authors	12
Source Title	Free Radical Biology and Medicine. - : Elsevier - ISSN 0891-5849 Roč. 162, č. 2021 (2021)
Number of pages	13 s.
Publication form	Print - P
Language	eng - English
Country	US - United States
Keywords	junctions ; Myeloperoxidase ; Inflammation ; Cardiovascular diseases ; Glycocalyx ; Endothelial cells
Subject RIV	CE - Biochemistry
OECD category	Biochemistry and molecular biology
Method of publishing	Limited access
Institutional support	BFU-R - RVO:68081707
UT WOS	000618526500002
EID SCOPUS	85097752050
DOI	10.1016/j.freeradbiomed.2020.11.008
Annotation	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.
Workplace	Institute of Biophysics
Contact	Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244
Year of Publishing	2022
Electronic address	https://www.sciencedirect.com/science/article/pii/S0891584920316063?via%3Dihub

Number of the records: 1