Myeloperoxidase mediated alteration of endothelial function is dependent on its cationic charge
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00541966" target="_blank" >RIV/68081707:_____/21:00541966 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14740/21:00121039
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0891584920316063?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0891584920316063?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.freeradbiomed.2020.11.008" target="_blank" >10.1016/j.freeradbiomed.2020.11.008</a>
Alternative languages
Result language
angličtina
Original language name
Myeloperoxidase mediated alteration of endothelial function is dependent on its cationic charge
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LM2018127" target="_blank" >LM2018127: Czech Infrastructure for Integrative Structural Biology</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Free Radical Biology and Medicine
ISSN
0891-5849
e-ISSN
1873-4596
Volume of the periodical
162
Issue of the periodical within the volume
2021
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
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UT code for WoS article
000618526500002
EID of the result in the Scopus database
2-s2.0-85097752050