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dc.contributor.authorHolte, Christopher Florian
dc.contributor.authorSzafranska, Karolina Joanna
dc.contributor.authorKruse, Larissa Dorothea
dc.contributor.authorSimon-Santamaria, Jaione
dc.contributor.authorLi, Ruomei
dc.contributor.authorSvistounov, Dmitri
dc.contributor.authorMcCourt, Peter Anthony
dc.date.accessioned2023-12-21T10:06:11Z
dc.date.available2023-12-21T10:06:11Z
dc.date.issued2023-11-05
dc.description.abstractOxidized albumin (oxHSA) is elevated in several pathological conditions, such as decompensated cirrhosis, acute on chronic liver failure and liver mediated renal failure. Patient derived oxidized albumin was previously shown to be an infammatory mediator, and in normal serum levels of oxHSA are low. The removal from circulation of oxidized albumins is therefore likely required for maintenance of homeostasis. Liver sinusoidal endothelial cells (LSEC) are prominent scavenger cells specialized in removal of macromolecular waste. Given that oxidized albumin is mainly cleared by the liver, we hypothesized the LSEC are the site of uptake in the liver. In vivo oxHSA was cleared rapidly by the liver and distributed to mainly the LSEC. In in vitro studies LSEC endocytosed oxHSA much more than other cell populations isolated from the liver. Furthermore, it was shown that the uptake was mediated by the stabilins, by afnity chromatography-mass spectrometry, inhibiting uptake in LSEC with other stabilin ligands and showing uptake in HEK cells overexpressing stabilin-1 or -2. oxHSA also inhibited the uptake of other stabilin ligands, and a 2-h challenge with 100 µg/mL oxHSA reduced LSEC endocytosis by 60% up to 12 h after. Thus the LSEC and their stabilins mediate clearance of highly oxidized albumin, and oxidized albumin can downregulate their endocytic capacity in turn.en_US
dc.identifier.citationHolte C, Szafranska KJ, Kruse LD, Simon-Santamaria J, Li R, Svistounov D, McCourt PAG. Highly oxidized albumin is cleared by liver sinusoidal endothelial cells via the receptors stabilin-1 and -2. Scientific Reports. 2023;13(1)en_US
dc.identifier.cristinIDFRIDAID 2200378
dc.identifier.doi10.1038/s41598-023-46462-9
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/10037/32194
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofHolte, C.F. (2024). Novel insights into the fenestrated scavenger endothelium of the liver sinusoid. (Doctoral thesis). <a href=https://hdl.handle.net/10037/33068>https://hdl.handle.net/10037/33068</a>
dc.relation.journalScientific Reports
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/101046928/EU/Long-term Microphysiological Sample Imaging for Evaluation of Polypharmacy in Liver/DeLIVERY/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/766181/EU/Super-resolution optical microscopy of nanosized pore dynamics in endothelial cells/DeLIVER/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleHighly oxidized albumin is cleared by liver sinusoidal endothelial cells via the receptors stabilin-1 and -2en_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
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