ArticleTransplantation direct2018
Endothelial Dysfunction in Steatotic Human Donor Livers: A Pilot Study of the Underlying Mechanism During Subnormothermic Machine Perfusion.
Article in Transplantation direct, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Use of machine perfusion in livers showing steatosis prior to transplantation: a systematic review.Updates in surgery · 2020Pooled it
- Hypothermic oxygenated perfusion inhibits CLIP1-mediated TIRAP ubiquitination via TFPI2 to reduce ischemia‒reperfusion injury of the fatty liver.Experimental & molecular medicine · 2024Article
- How to Preserve Steatotic Liver Grafts for Transplantation.Journal of clinical medicine · 2023Review
- Hypothermic Oxygenated Machine Perfusion of Liver Grafts from Brain-Dead Donors.Scientific reports · 2019Article
- Organ Preservation into the 2020s: The Era of Dynamic Intervention.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2019Review
- Glycocalyx Preservation and NO Production in Fatty Livers-The Protective Role of High Molecular Polyethylene Glycol in Cold Ischemia Injury.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSteatosis is a major risk factor for primary nonfunction in liver transplantations. Steatotic livers recover poorly from ischemia reperfusion injury, in part due to alterations in the microcirculation, although the exact mechanism is unclear. In this study, we tested if there were any alterations in the shear stress sensing Kruppel-like factor 2 (KLF2) and its likely downstream consequences in the ex vivo perfused human liver endothelium, which would imply perturbations in microcirculatory flow in macrosteatotic livers disrupts laminar flow to evaluate if this is a potential therapeutic target for steatotic livers.
methodsUsing a subnormothermic machine perfusion system, 5 macrosteatotic and 4 nonsteatotic human livers were perfused for 3 hours. Flow, resistance, and biochemical profile were monitored. Gene expression levels of nitric oxide synthase 3 (eNOS), KLF2, and thrombomodulin were determined. Nitric oxide (NO) was measured in the perfusion fluid and activation of eNOS was measured with Western blotting.
resultsFlow dynamics, injury markers, and bile production were similar in both groups. Kruppel-like factor 2 expression was significantly higher in nonsteatotic livers. Western blotting analyses showed significantly higher levels of activated eNOS in nonsteatotic livers, consistent with an increase in NO production over time. Macrosteatotic livers showed decreased KLF2 upregulation, eNOS activity, and NO production during machine perfusion.
conclusionsThese results indicate a perturbed KLF2 sensing in steatotic livers, which aligns with perturbed microcirculatory state. This may indicate endothelial dysfunction and contribute to poor posttransplantation outcomes in fatty livers, and further studies to confirm by evaluation of flow and testing treatments are warranted.
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Registered trials
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