Effects of circulating HMGB-1 and histones on cardiomyocytes−hemadsorption of these DAMPs as therapeutic strategy after multiple trauma
- Background and purpose: The aim of the study was to determine the effects of post-traumatically released High Mobility Group Box-1 protein (HMGB1) and extracellular histones on cardiomyocytes (CM). We also evaluated a therapeutic option to capture circulating histones after trauma, using a hemadsorption filter to treat CM dysfunction. Experimental Approach: We evaluated cell viability, calcium handling and mitochondrial respiration of human cardiomyocytes in the presence of HMGB-1 and extracellular histones. In a translational approach, a hemadsorption filter was applied to either directly eliminate extracellular histones or to remove them from blood samples obtained from multiple injured patients. Key results: Incubation of human CM with HMGB-1 or histones is associated with changes in calcium handling, a reduction of cell viability and a substantial reduction of the mitochondrial respiratory capacity. Filtrating plasma from injured patients with a hemadsorption filter reduces histone concentration ex vivo and in vitro, depending on dosage. Conclusion and implications: Danger associated molecular patterns such as HMGB-1 and extracellular histones impair human CM in vitro. A hemadsorption filter could be a therapeutic option to reduce high concentrations of histones.
Verfasserangaben: | Birte WeberORCiDGND, Ina Lackner, Meike Baur, Giorgio FoisORCiDGND, Florian Gebhard, Ingo MarziORCiDGND, Hubert SchrezenmeierORCiDGND, Borna ReljaORCiDGND, Miriam KalbitzORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-548140 |
DOI: | https://doi.org/10.3390/jcm9051421 |
ISSN: | 2077-0383 |
Titel des übergeordneten Werkes (Englisch): | Journal of clinical medicine |
Verlag: | MDPI |
Verlagsort: | Ba |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 11.05.2020 |
Datum der Erstveröffentlichung: | 11.05.2020 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 11.06.2020 |
Freies Schlagwort / Tag: | DAMPs; calcium handling; early myocardial damage (EMD); hemadsorption; mitochondrial dysfunction; post-traumatic |
Jahrgang: | 9 |
Ausgabe / Heft: | 1421 |
Seitenzahl: | 13 |
HeBIS-PPN: | 467140502 |
Institute: | Medizin / Medizin |
DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | Creative Commons - Namensnennung 4.0 |