MPO (Myeloperoxidase) Reduces Endothelial Glycocalyx Thickness Dependent on Its Cationic Charge

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F18%3A00069324" target="_blank" >RIV/00159816:_____/18:00069324 - isvavai.cz</a>

Alternative codes found

RIV/68081707:_____/18:00495517

Result on the web

<a href="http://dx.doi.org/10.1161/ATVBAHA.118.311143" target="_blank" >http://dx.doi.org/10.1161/ATVBAHA.118.311143</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1161/ATVBAHA.118.311143" target="_blank" >10.1161/ATVBAHA.118.311143</a>

Result language

angličtina

Original language name

MPO (Myeloperoxidase) Reduces Endothelial Glycocalyx Thickness Dependent on Its Cationic Charge

Original language description

Objective The leukocyte heme-enzyme MPO (myeloperoxidase) exerts proinflammatory effects on the vascular system primarily linked to its catalytic properties. Recent studies have shown that MPO, depending on its cationic charge, mediates neutrophil recruitment and activation. Here, we further investigated MPO&apos;s extracatalytic properties and its effect on endothelial glycocalyx (EG) integrity. Approach and Results In vivo staining of murine cremaster muscle vessels with Alcian Blue 8GX provided evidence of an MPO-dependent decrease in anionic charge of the EG. MPO binding to the glycocalyx was further characterized using Chinese hamster ovary cells and its glycosaminoglycan mutantspgsA-745 (mutant Chinese hamster ovary cells lacking heparan sulfate and chondroitin sulfate glycosaminoglycan) and pgsD-677 (mutant Chinese hamster ovary cells lacking heparan sulfate glycosaminoglycan), which revealed heparan sulfate as the main mediator of MPO binding. Further, EG integrity was assessed in terms of thickness using intravital microscopy of murine cremaster muscle. A significant reduction in EG thickness was observed on infusion of catalytically active MPO, as well as mutant inactive MPO and cationic polymer polylysine. Similar effects were also observed in wild-type mice after a local inflammatory stimulus but not in MPO-knockout mice. The reduction in EG thickness was reversed after removal of vessel-bound MPO, suggesting a possible physical collapse of the EG. Last, experiments with in vivo neutrophil depletion revealed that MPO also induced neutrophil-mediated shedding of the EG core protein, Sdc1 (syndecan-1). Conclusions These findings provide evidence that MPO, via ionic interaction with heparan sulfate side chains, can cause neutrophil-dependent Sdc1 shedding and collapse of the EG structure.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30205 - Hematology

Project

<a href="/en/project/LQ1605" target="_blank" >LQ1605: Translational Medicine</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Arteriosclerosis thrombosis and vascular biology

ISSN

1079-5642

e-ISSN

—

Volume of the periodical

38

Issue of the periodical within the volume

8

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

1859-1867

UT code for WoS article

000439942200021

EID of the result in the Scopus database

—