Impact of oxidized low-density lipoprotein on rat liver sinusoidal endothelial cell morphology and function
Abstract Atherogenesis is associated with elevated plasma levels of oxidized low-density lipoproteins (oxLDL). In vivo, oxLDL causes liver endothelial swelling, and disrupts liver sinusoidal endothelial cell (LSECs) fenestrations. We mapped the nanoscale kinetics of these changes in vitro in isolated rat LSECs challenged with oxLDL and monitored viability with endocytosis and cytotoxicity assays. OxLDL disrupted LSEC ultrastructure – increasing oxLDL concentrations and oxidation levels caused sieve plate loss, fenestration fusion, and gap formation. Importantly, these effects were not uniform across all LSECs. LSECs retained the ability to endocytose ligands irrespective of the presence of oxLDL. However, increasing oxidation levels and concentrations of oxLDL inhibited LSEC mediated degradation of endocytosed ligands. Viability was unaffected by any oxLDL challenge. In conclusion, oxLDL disrupts LSEC ultrastructural morphology in vitro but LSECs remain viable and mostly maintain the scavenging function during oxLDL challenge.
Authors
- Wolfgang Hübner (ORCID: https://orcid.org/0000-0002-1128-6468)
- Cristina Ionica Øie (ORCID: https://orcid.org/0000-0001-6576-9118)
- Thomas Huser (ORCID: https://orcid.org/0000-0003-2348-7416)
- Larissa D. Kruse (ORCID: https://orcid.org/0000-0002-2015-2293)
- Ana Oteiza (ORCID: https://orcid.org/0009-0007-2246-6927)
- Hong Mao
- David G. Le Couteur (ORCID: https://orcid.org/0000-0002-4227-5817)
- Peter McCourt (ORCID: https://orcid.org/0000-0001-5072-4590)
- Deanna L. Wolfson (ORCID: https://orcid.org/0000-0001-6059-2472)
- Balpreet Singh Ahluwalia (ORCID: https://orcid.org/0000-0001-7841-6952)
- Victoria C. Cogger (ORCID: https://orcid.org/0000-0002-6346-9928)
- Ruomei Li (ORCID: https://orcid.org/0000-0003-0213-3301)
- Jasmin Schürstedt (ORCID: https://orcid.org/0009-0008-6067-1806)
- Eike C. Struck
Institutions
- The University of Sydney (AU)
- University Hospital of North Norway (NO)
- Bielefeld University (DE)
- Concord Repatriation General Hospital (AU)
- UiT The Arctic University of Norway (NO)
Publication Details
- Journal
- npj gut and liver.
- Published
- 2024-10-23
- DOI
- https://doi.org/10.1038/s44355-024-00009-5
- Citations
- 4
- Primary Topic
- Kruppel-like factors research
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- Universitetet i Tromsø
- Tromsø Forskningsstiftelse
- Norges Forskningsråd
- H2020 Marie Skłodowska-Curie Actions
- HORIZON EUROPE European Innovation Council