Chronic heart failure induces early defenestration of liver sinusoidal endothelial cells (LSECs) in mice

2024
journal article
article
3
cris.lastimport.wos2024-04-09T19:39:06Z
dc.abstract.enChronic heart failure (CHF) is often linked to liver malfunction and systemic endothelial dysfunction. However, whether cardio-hepatic interactions in heart failure involve dysfunction of liver sinusoidal endothelial cells (LSECs) is not known. Here we characterize LSECs phenotype in early and end stages of chronic heart failure in a murine model. Right ventricle (RV) function, features of congestive hepatopathy, and the phenotype of primary LSECs were characterized in $Tg\alpha q^{*}44$ mice, with cardiomyocyte-specific overexpression of the Gαq protein, at the age of 4- and 12-month representative for early and end-stage phases of CHF, respectively. 4- and 12-month-old $Tg\alpha q^{*}44$ mice displayed progressive impairment of RV function and alterations in hepatic blood flow velocity resulting in hepatic congestion with elevated GGT and bilirubin plasma levels and decreased albumin concentration without gross liver pathology. LSECs isolated from 4- and 12-month-old $Tg\alpha q^{*}44$ mice displayed significant loss of fenestrae with impaired functional response to cytochalasin B, significant changes in proteome related to cytoskeleton remodeling, and altered vasoprotective function. However, LSECs barrier function and bioenergetics were largely preserved. In 4- and 12-month-old $Tg\alpha q^{*}44$ mice, LSECs defenestration was associated with prolonged postprandial hypertriglyceridemia and in 12-month-old $Tg\alpha q^{*}44$ mice with proteomic changes of hepatocytes indicative of altered lipid metabolism. $Tg\alpha q^{*}44$ mice displayed right-sided HF and altered hepatic blood flow leading to LSECs dysfunction involving defenestration, shift in eicosanoid profile, and proteomic changes. LSECs dysfunction appears as an early and persistent event in CHF, preceding congestive hepatopathy and contributing to alterations in lipoprotein transport and CHF pathophysiology.pl
dc.affiliationPion Prorektora ds. badań naukowych : Jagiellońskie Centrum Rozwoju Lekówpl
dc.affiliationWydział Lekarski : Zakład Farmakologiipl
dc.affiliationWydział Fizyki, Astronomii i Informatyki Stosowanej : Instytut Fizyki im. Mariana Smoluchowskiegopl
dc.cm.id114719
dc.cm.idOmegaUJCM945385dc51234541b2b3bb016ced3888pl
dc.contributor.authorWojnar-Lasoń, Kamila - 220138 pl
dc.contributor.authorTyrankiewicz, Urszula - 381603 pl
dc.contributor.authorKij, Agnieszka - 215016 pl
dc.contributor.authorKurpińska, Anna - 256178 pl
dc.contributor.authorKaczara, Patrycja - 200164 pl
dc.contributor.authorKwiatkowski, Grzegorz - 149211 pl
dc.contributor.authorWilkosz, Natalia - 169289 pl
dc.contributor.authorGiergiel, Magdalena - 163128 pl
dc.contributor.authorStojak, Marta - 104367 pl
dc.contributor.authorGrosicki, Marek - 219940 pl
dc.contributor.authorMohaissen, Tasnim - 193046 pl
dc.contributor.authorJasztal, Agnieszka - 129875 pl
dc.contributor.authorKuryłowicz, Zuzanna - 259430 pl
dc.contributor.authorSzymoński, Marek - 132296 pl
dc.contributor.authorCzyżyńska-Cichoń, Izabela - 364284 pl
dc.contributor.authorChłopicki, Stefan - 128995 pl
dc.date.accession2024-03-20pl
dc.date.accessioned2024-03-06T12:50:59Z
dc.date.available2024-03-06T12:50:59Z
dc.date.issued2024pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.additionalOnline First 2024-02-23pl
dc.description.number5pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume240pl
dc.identifier.articleide14114pl
dc.identifier.doi10.1111/apha.14114pl
dc.identifier.eissn1748-1716pl
dc.identifier.issn1748-1708pl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/327699
dc.identifier.weblinkhttps://onlinelibrary.wiley.com/doi/10.1111/apha.14114pl
dc.languageengpl
dc.language.containerengpl
dc.pbn.affiliationDziedzina nauk medycznych i nauk o zdrowiu : nauki medyczne
dc.rightsUdzielam licencji. Uznanie autorstwa - Użycie niekomercyjne - Bez utworów zależnych 4.0 Międzynarodowa*
dc.rights.licenceCC-BY-NC-ND
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/legalcode.pl*
dc.share.typeOtwarte czasopismo
dc.subject.encardio-hepatic interactionspl
dc.subject.enchronic heart failurepl
dc.subject.enfenestrationspl
dc.subject.enliver sinusoidal endothelial cellspl
dc.subject.enLSECspl
dc.subtypeArticlepl
dc.titleChronic heart failure induces early defenestration of liver sinusoidal endothelial cells (LSECs) in micepl
dc.title.journalActa Physiologicapl
dc.typeJournalArticlepl
dspace.entity.typePublication
cris.lastimport.wos
2024-04-09T19:39:06Z
dc.abstract.enpl
Chronic heart failure (CHF) is often linked to liver malfunction and systemic endothelial dysfunction. However, whether cardio-hepatic interactions in heart failure involve dysfunction of liver sinusoidal endothelial cells (LSECs) is not known. Here we characterize LSECs phenotype in early and end stages of chronic heart failure in a murine model. Right ventricle (RV) function, features of congestive hepatopathy, and the phenotype of primary LSECs were characterized in $Tg\alpha q^{*}44$ mice, with cardiomyocyte-specific overexpression of the Gαq protein, at the age of 4- and 12-month representative for early and end-stage phases of CHF, respectively. 4- and 12-month-old $Tg\alpha q^{*}44$ mice displayed progressive impairment of RV function and alterations in hepatic blood flow velocity resulting in hepatic congestion with elevated GGT and bilirubin plasma levels and decreased albumin concentration without gross liver pathology. LSECs isolated from 4- and 12-month-old $Tg\alpha q^{*}44$ mice displayed significant loss of fenestrae with impaired functional response to cytochalasin B, significant changes in proteome related to cytoskeleton remodeling, and altered vasoprotective function. However, LSECs barrier function and bioenergetics were largely preserved. In 4- and 12-month-old $Tg\alpha q^{*}44$ mice, LSECs defenestration was associated with prolonged postprandial hypertriglyceridemia and in 12-month-old $Tg\alpha q^{*}44$ mice with proteomic changes of hepatocytes indicative of altered lipid metabolism. $Tg\alpha q^{*}44$ mice displayed right-sided HF and altered hepatic blood flow leading to LSECs dysfunction involving defenestration, shift in eicosanoid profile, and proteomic changes. LSECs dysfunction appears as an early and persistent event in CHF, preceding congestive hepatopathy and contributing to alterations in lipoprotein transport and CHF pathophysiology.
dc.affiliationpl
Pion Prorektora ds. badań naukowych : Jagiellońskie Centrum Rozwoju Leków
dc.affiliationpl
Wydział Lekarski : Zakład Farmakologii
dc.affiliationpl
Wydział Fizyki, Astronomii i Informatyki Stosowanej : Instytut Fizyki im. Mariana Smoluchowskiego
dc.cm.id
114719
dc.cm.idOmegapl
UJCM945385dc51234541b2b3bb016ced3888
dc.contributor.authorpl
Wojnar-Lasoń, Kamila - 220138
dc.contributor.authorpl
Tyrankiewicz, Urszula - 381603
dc.contributor.authorpl
Kij, Agnieszka - 215016
dc.contributor.authorpl
Kurpińska, Anna - 256178
dc.contributor.authorpl
Kaczara, Patrycja - 200164
dc.contributor.authorpl
Kwiatkowski, Grzegorz - 149211
dc.contributor.authorpl
Wilkosz, Natalia - 169289
dc.contributor.authorpl
Giergiel, Magdalena - 163128
dc.contributor.authorpl
Stojak, Marta - 104367
dc.contributor.authorpl
Grosicki, Marek - 219940
dc.contributor.authorpl
Mohaissen, Tasnim - 193046
dc.contributor.authorpl
Jasztal, Agnieszka - 129875
dc.contributor.authorpl
Kuryłowicz, Zuzanna - 259430
dc.contributor.authorpl
Szymoński, Marek - 132296
dc.contributor.authorpl
Czyżyńska-Cichoń, Izabela - 364284
dc.contributor.authorpl
Chłopicki, Stefan - 128995
dc.date.accessionpl
2024-03-20
dc.date.accessioned
2024-03-06T12:50:59Z
dc.date.available
2024-03-06T12:50:59Z
dc.date.issuedpl
2024
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.additionalpl
Online First 2024-02-23
dc.description.numberpl
5
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
240
dc.identifier.articleidpl
e14114
dc.identifier.doipl
10.1111/apha.14114
dc.identifier.eissnpl
1748-1716
dc.identifier.issnpl
1748-1708
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/327699
dc.identifier.weblinkpl
https://onlinelibrary.wiley.com/doi/10.1111/apha.14114
dc.languagepl
eng
dc.language.containerpl
eng
dc.pbn.affiliation
Dziedzina nauk medycznych i nauk o zdrowiu : nauki medyczne
dc.rights*
Udzielam licencji. Uznanie autorstwa - Użycie niekomercyjne - Bez utworów zależnych 4.0 Międzynarodowa
dc.rights.licence
CC-BY-NC-ND
dc.rights.uri*
http://creativecommons.org/licenses/by-nc-nd/4.0/legalcode.pl
dc.share.type
Otwarte czasopismo
dc.subject.enpl
cardio-hepatic interactions
dc.subject.enpl
chronic heart failure
dc.subject.enpl
fenestrations
dc.subject.enpl
liver sinusoidal endothelial cells
dc.subject.enpl
LSECs
dc.subtypepl
Article
dc.titlepl
Chronic heart failure induces early defenestration of liver sinusoidal endothelial cells (LSECs) in mice
dc.title.journalpl
Acta Physiologica
dc.typepl
JournalArticle
dspace.entity.type
Publication

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