Therapeutic hyperthermia promotes lipid export and HSP70/90 during machine perfusion of human livers.

Publisher: published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society Country of Publication: United States NLM ID: 101607800 Publication Model: Print Cited Medium: Internet ISSN: 2051-817X (Electronic) Linking ISSN: 2051817X NLM ISO Abbreviation: Physiol Rep Subsets: MEDLINE

Original Publication: [Malden MA] : published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society, 2013-

Liver*/metabolism ; Hyperthermia, Induced*/methods ; HSP70 Heat-Shock Proteins*/metabolism ; Lipid Metabolism*; Perfusion/methods ; Liver Transplantation/methods ; Fatty Liver/metabolism ; Fatty Liver/therapy ; Organ Preservation/methods ; Humans ; Male ; Middle Aged ; Female ; Adult

Liver transplantation is the only curative option for end-stage liver disease. Donor shortages necessitate the use of higher risk donor livers, including fatty livers, which are more susceptible to ischemia-reperfusion injury. Machine perfusion has improved graft utilization and is typically performed at hypothermic (8-12°C) or normothermic (35-37°C) temperatures. Here we studied the impact of mild hyperthermia (40°C) as a therapeutic intervention for fatty livers using in-depth proteomic and lipoprotein profiling of whole organ perfusion and precision-cut liver slices. We observed proteomic changes with metabolic alterations over time, evidenced by a significant increase in lipid export in whole organ perfusions. Furthermore, PCLS showed significant upregulation of metabolic processes and heat shock protein response after 24 h of hyperthermia. Machine perfusion under hyperthermic conditions may be a potential strategy to improve the utilization of fatty liver grafts, ultimately expanding the donor pool and improving transplant outcomes.
(© 2025 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

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09150161810030 Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO); PPP31 2019-024 Ministerie van Economische Zaken en Klimaat (EZK); 01-2021 Nederlandse Vereniging voor Gastroenterologie (NVGE); Noaber Foundation (NF)

Keywords: hyperthermia; lipids; liver; machine perfusion; proteomics

0 (HSP70 Heat-Shock Proteins)

Date Created: 20250509 Date Completed: 20250510 Latest Revision: 20250512

20260130

PMC12064339

10.14814/phy2.70348

40346031