دورية أكاديمية
Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction
| العنوان: | Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction |
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| المؤلفون: | Jakobsson, Gabriel, Papareddy, Praveen, Andersson, Henrik, Mulholland, Megan, Bhongir, Ravi Kiran Varma, Ljungcrantz, Irena, Ruiz Meana, Marisol, Rodriguez-Sinovas, Antonio |
| المساهمون: | Institut Català de la Salut, Jakobsson G Department of Translational Medicine, Lund University, Lund, Sweden. Cardiac Infammation Research Group, Clinical Research Center, Malmö, Sweden. Papareddy P, Bhongir R Department of Clinical Sciences Lund, Lund University, Lund, Sweden. Andersson H Department of Anaesthesia and Intensive Care, Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden. Mulholland M, Ljungcrantz I Department of Clinical Sciences Malmö, Lund University, Lund, Sweden. Ruiz-Meana M, Rodríguez-Sinovas A Grup de Recerca de Malalties Cardiovasculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | BMC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Inflamació, Cor - Malalties - Tractament, Septicèmia, DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation::Systemic Inflammatory Response Syndrome::Sepsis, DISEASES::Cardiovascular Diseases::Heart Diseases, Signs and Symptoms::Pathologic Processes::Inflammation, Other subheadings::Other subheadings::Other subheadings::/drug therapy, ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::inflamación::síndrome de respuesta inflamatoria sistémica::sepsis, ENFERMEDADES::enfermedades cardiovasculares::enfermedades cardíacas, signos y síntomas::procesos patológicos::inflamación, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia |
| الوصف: | Endotoxemia; Inflammation; Mitochondrial function ; Endotoxemia; Inflamación; Función mitocondrial ; Endotoxèmia; Inflamació; Funció mitocondrial ; Background and Aims The triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory alarmin abundantly secreted by activated neutrophils during infection and inflammation. We investigated the efficacy of S100A8/A9 blockade as a potential new treatment in SIMD. Methods The relationship between plasma S100A8/A9 and cardiac dysfunction was assessed in a cohort of 62 patients with severe sepsis admitted to the intensive care unit of Linköping University Hospital, Sweden. We used S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 and S100A9−/− mice for therapeutic and mechanistic studies on endotoxemia-induced cardiac dysfunction in mice. Results In sepsis patients, elevated plasma S100A8/A9 was associated with left-ventricular (LV) systolic dysfunction and increased SOFA score. In wild-type mice, 5 mg/kg of bacterial lipopolysaccharide (LPS) induced rapid plasma S100A8/A9 increase and acute LV dysfunction. Two ABR-238901 doses (30 mg/kg) administered intraperitoneally with a 6 h interval, starting directly after LPS or at a later time-point when LV dysfunction is fully established, efficiently prevented and reversed the phenotype, respectively. In contrast, dexamethasone did not improve cardiac function compared to PBS-treated endotoxemic controls. S100A8/A9 inhibition potently reduced systemic levels of inflammatory mediators, prevented upregulation of inflammatory genes and restored mitochondrial function in the myocardium. The S100A9−/− mice were protected against LPS-induced LV dysfunction to an extent comparable with pharmacologic S100A8/A9 blockade. The ABR-238901 treatment did not induce an additional improvement of LV function in the S100A9−/− mice, confirming target specificity. Conclusion Elevated S100A8/A9 is associated with the development of ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1364-8535 37773186 |
| العلاقة: | Critical care : the official journal of the Critical Care Forum;27; https://doi.org/10.1186/s13054-023-04652-xTest; Jakobsson G, Papareddy P, Andersson H, Mulholland M, Bhongir R, Ljungcrantz I, et al. Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction. Crit Care. 2023 Sep 29;27:374.; https://hdl.handle.net/11351/10415Test |
| DOI: | 10.1186/s13054-023-04652-x |
| الإتاحة: | https://doi.org/10.1186/s13054-023-04652-xTest https://hdl.handle.net/11351/10415Test |
| حقوق: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E3A8BA4B |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 13648535 37773186 |
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| DOI: | 10.1186/s13054-023-04652-x |