TY - JOUR A1 - Weber, Birte A1 - Lackner, Ina A1 - Baur, Meike A1 - Fois, Giorgio A1 - Gebhard, Florian A1 - Marzi, Ingo A1 - Schrezenmeier, Hubert A1 - Relja, Borna A1 - Kalbitz, Miriam T1 - Effects of circulating HMGB-1 and histones on cardiomyocytes−hemadsorption of these DAMPs as therapeutic strategy after multiple trauma T2 - Journal of clinical medicine N2 - 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. KW - hemadsorption KW - early myocardial damage (EMD) KW - DAMPs KW - post-traumatic KW - calcium handling KW - mitochondrial dysfunction Y1 - 2020 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/54814 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-548140 SN - 2077-0383 VL - 9 IS - 1421 PB - MDPI CY - Ba ER -