Abstract | 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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Authors | Birte Weber, Ina Lackner, Meike Baur, Giorgio Fois, Florian Gebhard, Ingo Marzi, Hubert Schrezenmeier, Borna Relja, Miriam Kalbitz |
Journal | Journal of clinical medicine
(J Clin Med)
Vol. 9
Issue 5
(May 11 2020)
ISSN: 2077-0383 [Print] Switzerland |
PMID | 32403440
(Publication Type: Journal Article)
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