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.

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Author:Birte Weber, Ina Lackner, Meike Baur, Giorgio Fois, Florian Gebhard, Ingo MarziORCiDGND, Hubert Schrezenmeier, Borna ReljaORCiDGND, Miriam Kalbitz
URN:urn:nbn:de:hebis:30:3-548140
DOI:https://doi.org/10.3390/jcm9051421
ISSN:2077-0383
Parent Title (English):Journal of clinical medicine
Publisher:MDPI
Place of publication:Ba
Document Type:Article
Language:English
Date of Publication (online):2020/05/11
Date of first Publication:2020/05/11
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/06/11
Tag:DAMPs; calcium handling; early myocardial damage (EMD); hemadsorption; mitochondrial dysfunction; post-traumatic
Volume:9
Issue:1421
Page Number:13
HeBIS-PPN:467140502
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0