Succinate Activation of SUCNR1 Predisposes Severely Injured Patients to Neutrophil-mediated ARDS
| Autor: | Xiayuan Liang, Carter Jones, Mitchell J. Cohen, Geoffrey R. Nunns, Anirban Banerjee, Angela Sauaia, Andrew P. Eitel, Christopher C. Silliman, Lajos Gera, Erik D. Peltz, Arsen Ghasabyan, Fabia Gamboni, James G. Chandler, Patrick Hom, Gregory R. Stettler, Kirk C. Hansen, Angelo D'Alessandro, Kenneth L. Jones, Julie A. Reisz, Joshua J. Ryon, Marguerite R. Kelher, Ernest E. Moore, Sophia Rodawig, Navin G. Vigneshwar |
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| Rok vydání: | 2020 |
| Předmět: |
ARDS
Lipopolysaccharide Neutrophils Succinic Acid Pharmacology Creatine Article Pulmonary sequestration 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Animals Medicine Bronchopulmonary Sequestration Receptor Lung Respiratory Distress Syndrome business.industry medicine.disease medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis 030211 gastroenterology & hepatology Surgery business Intracellular |
| Zdroj: | Ann Surg |
| ISSN: | 0003-4932 |
| DOI: | 10.1097/sla.0000000000004644 |
| Popis: | OBJECTIVES: Identify the metabolites that are increased in the plasma of severely injured patients that developed ARDS versus severely injured patients that did not, and assay if these increased metabolites prime PMNs and induce pulmonary sequestration in an animal model of ARDS. We hypothesize that metabolic derangement due to advanced shock in critically injured patients leads to the pulmonary sequestration of neutrophils (PMNs), which serves as the first event in the acute respiratory distress syndrome (ARDS). SUMMARY BACKGROUND DATA: Intracellular metabolites accumulate in the plasma of severely injured patients. METHODS: Untargeted metabolomics profiling of 67 critically injured patients was completed to establish a metabolic signature associated with ARDS development. Metabolites that signficantly increased were assayed for PMN priming activity in vitro. The metabolites that primed PMNs were tested in a two-event animal model of ARDS to identify a molecular link between circulating metabolites and clinical risk for ARDS. RESULTS: After controlling for confounders, four metabolites significantly increased: creatine, dehydroascorbate, fumarate, and succinate in trauma patients who developed ARDS (p |
| Databáze: | OpenAIRE |
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