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

J 2021

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

KOLÁŘOVÁ, Hana, Jan VÍTEČEK, Anna ČERNÁ, Marek ČERNÍK, Jan PŘIBYL et. al.

Basic information

Original name

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

Authors

KOLÁŘOVÁ, Hana, Jan VÍTEČEK, Anna ČERNÁ, Marek ČERNÍK (203 Czech Republic), Jan PŘIBYL (203 Czech Republic, belonging to the institution), Petr SKLÁDAL (203 Czech Republic, belonging to the institution), David POTĚŠIL (203 Czech Republic, belonging to the institution), Ivana IHNATOVÁ (703 Slovakia, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, belonging to the institution), Aleš HAMPL (203 Czech Republic, belonging to the institution), Anna KLINKE and Lukáš KUBALA (guarantor)

Edition

Free Radical Biology and Medicine, New York, Elsevier, 2021, 0891-5849

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 8.101

RIV identification code

RIV/00216224:14740/21:00121039

Organization unit

Central European Institute of Technology

DOI

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

UT WoS

000618526500002

Keywords in English

Myeloperoxidase; Inflammation; Cardiovascular diseases; Glycocalyx; Endothelial cells; Proteomic analysis; Glycosaminoglycan; Vascular inflammation

Abstract

V originále

Endothelial cell (EC) glycocalyx (GLX) comprise a multicomponent layer of proteoglycans 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.

Links

LM2018127, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

90127, large research infrastructures

Name: CIISB II

Citovat

KOLÁŘOVÁ, Hana, Jan VÍTEČEK, Anna ČERNÁ, Marek ČERNÍK, Jan PŘIBYL, Petr SKLÁDAL, David POTĚŠIL, Ivana IHNATOVÁ, Zbyněk ZDRÁHAL, Aleš HAMPL, Anna KLINKE and Lukáš KUBALA. Myeloperoxidase mediated alteration of endothelial function is dependent on its cationic charge. Free Radical Biology and Medicine. New York: Elsevier, 2021, vol. 162, January 2021, p. 14-26. ISSN 0891-5849. Available from: https://dx.doi.org/10.1016/j.freeradbiomed.2020.11.008.

@article{1734582,
   author = {Kolářová, Hana and Víteček, Jan and Černá, Anna and Černík, Marek and Přibyl, Jan and Skládal, Petr and Potěšil, David and Ihnatová, Ivana and Zdráhal, Zbyněk and Hampl, Aleš and Klinke, Anna and Kubala, Lukáš},
   article_location = {New York},
   article_number = {January 2021},
   doi = {http://dx.doi.org/10.1016/j.freeradbiomed.2020.11.008},
   keywords = {Myeloperoxidase; Inflammation; Cardiovascular diseases; Glycocalyx; Endothelial cells; Proteomic analysis; Glycosaminoglycan; Vascular inflammation},
   language = {eng},
   issn = {0891-5849},
   journal = {Free Radical Biology and Medicine},
   title = {Myeloperoxidase mediated alteration of endothelial function is dependent on its cationic charge},
   url = {https://doi.org/10.1016/j.freeradbiomed.2020.11.008},
   volume = {162},
   year = {2021}
}

TY  - JOUR
ID  - 1734582
AU  - Kolářová, Hana - Víteček, Jan - Černá, Anna - Černík, Marek - Přibyl, Jan - Skládal, Petr - Potěšil, David - Ihnatová, Ivana - Zdráhal, Zbyněk - Hampl, Aleš - Klinke, Anna - Kubala, Lukáš
PY  - 2021
TI  - Myeloperoxidase mediated alteration of endothelial function is dependent on its cationic charge
JF  - Free Radical Biology and Medicine
VL  - 162
IS  - January 2021
SP  - 14-26
EP  - 14-26
PB  - Elsevier
SN  - 08915849
KW  - Myeloperoxidase
KW  - Inflammation
KW  - Cardiovascular diseases
KW  - Glycocalyx
KW  - Endothelial cells
KW  - Proteomic analysis
KW  - Glycosaminoglycan
KW  - Vascular inflammation
UR  - https://doi.org/10.1016/j.freeradbiomed.2020.11.008
L2  - https://doi.org/10.1016/j.freeradbiomed.2020.11.008
N2  - Endothelial cell (EC) glycocalyx (GLX) comprise a multicomponent layer of proteoglycans 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.
ER  -

KOLÁŘOVÁ, Hana, Jan VÍTEČEK, Anna ČERNÁ, Marek ČERNÍK, Jan PŘIBYL, Petr SKLÁDAL, David POTĚŠIL, Ivana IHNATOVÁ, Zbyněk ZDRÁHAL, Aleš HAMPL, Anna KLINKE and Lukáš KUBALA. Myeloperoxidase mediated alteration of endothelial function is dependent on its cationic charge. \textit{Free Radical Biology and Medicine}. New York: Elsevier, 2021, vol.~162, January 2021, p.~14-26. ISSN~0891-5849. Available from: https://dx.doi.org/10.1016/j.freeradbiomed.2020.11.008.

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