Effects of Circulating HMGB-1 and Histones on Cardiomyocytes–Hemadsorption of These DAMPs as Therapeutic Strategy after Multiple Trauma
Open Access
- 11 May 2020
- journal article
- research article
- Published by MDPI AG in Journal of Clinical Medicine
- Vol. 9 (5), 1421
- https://doi.org/10.3390/jcm9051421
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.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (CRC1149)
This publication has 56 references indexed in Scilit:
- Exogenous high-mobility group box 1 improves myocardial recovery after acute global ischemia/reperfusion injurySurgery, 2011
- TNF-α and IL-1β increase Ca2+ leak from the sarcoplasmic reticulum and susceptibility to arrhythmia in rat ventricular myocytesCell Calcium, 2010
- Extracellular histones are major mediators of death in sepsisNature Medicine, 2009
- Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusionCritical Care, 2009
- Fat tissue and adiponectin: new players in critical care?Critical Care, 2009
- Effects of hemoadsorption on cytokine removal and short-term survival in septic ratsCritical Care Medicine, 2008
- Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1)Angiogenesis, 2008
- High‐mobility group box 1 protein promotes development of microvascular thrombosis in ratsJournal of Thrombosis and Haemostasis, 2006
- Troponin Increases in the Critically Injured Patient: Mechanical Trauma or Physiologic Stress?Journal Of Trauma-Injury Infection and Critical Care, 2005
- Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-κB DNA binding, and improves short-term survival in lethal endotoxemia*Critical Care Medicine, 2004