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Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma

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dc.contributor.author Krocker, Joseph D.
dc.contributor.author Lee, Kyung Hyun
dc.contributor.author Henriksen, Hanne H.
dc.contributor.author Wang, Yao Wei Willa
dc.contributor.author Schoof, Erwin M.
dc.contributor.author Karvelsson, Sigurdur T.
dc.contributor.author Rolfsson, Óttar
dc.contributor.author Johansson, P. I.
dc.contributor.author Pedroza, Claudia
dc.contributor.author Wade, Charles E.
dc.date.accessioned 2023-01-25T01:05:08Z
dc.date.available 2023-01-25T01:05:08Z
dc.date.issued 2022-06-01
dc.identifier.citation Krocker , J D , Lee , K H , Henriksen , H H , Wang , Y W W , Schoof , E M , Karvelsson , S T , Rolfsson , Ó , Johansson , P I , Pedroza , C & Wade , C E 2022 , ' Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma ' , International Journal of Molecular Sciences , vol. 23 , no. 11 , 6213 . https://doi.org/10.3390/ijms23116213
dc.identifier.issn 1661-6596
dc.identifier.other PURE: 70209612
dc.identifier.other PURE UUID: f0aad2f3-ee4b-47ae-95b1-c1e577b762a1
dc.identifier.other Scopus: 85131705870
dc.identifier.uri https://hdl.handle.net/20.500.11815/3894
dc.description Funding Information: Funding: This work was supported by the National Institute of General Medical Sciences of the NIH (5T32GM008792). This project received funding from the William Stamps Farish Fund, the Howell Family Foundation, and the James H. “Red” Duke Professorship. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
dc.description.abstract Background: The endotheliopathy of trauma (EoT) is associated with increased mortality following injury. Herein, we describe the plasma proteome related to EoT in order to provide insight into the role of the endothelium within the systemic response to trauma. Methods: 99 subjects requiring the highest level of trauma activation were included in the study. Enzyme-linked immunosorbent assays of endothelial and catecholamine biomarkers were performed on admission plasma samples, as well as untargeted proteome quantification utilizing high-performance liquid chromatography and tandem mass spectrometry. Results: Plasma endothelial and catecholamine biomarker abundance was elevated in EoT. Patients with EoT (n = 62) had an increased incidence of death within 24 h at 21% compared to 3% for non-EoT (n = 37). Proteomic analysis revealed that 52 out of 290 proteins were differentially expressed between the EoT and non-EoT groups. These proteins are involved in endothelial activation, coagulation, inflammation, and oxidative stress, and include known damage-associated molecular patterns (DAMPs) and intracellular proteins specific to several organs. Conclusions: We report a proteomic profile of EoT suggestive of a surge of DAMPs and inflammation driving nonspecific activation of the endothelial, coagulation, and complement systems with subsequent end-organ damage and poor clinical outcome. These findings support the utility of EoT as an index of cellular injury and delineate protein candidates for therapeutic intervention.
dc.format.extent
dc.language.iso en
dc.relation.ispartofseries International Journal of Molecular Sciences; 23(11)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Coagulopathy
dc.subject Complement
dc.subject Damage-associated molecular patterns
dc.subject Endothelium
dc.subject Inflammation
dc.subject Proteomics
dc.subject Soluble thrombomodulin
dc.subject Sympathetic
dc.subject Syndecan-1
dc.subject Trauma
dc.subject Catalysis
dc.subject Molecular Biology
dc.subject Spectroscopy
dc.subject Computer Science Applications
dc.subject Physical and Theoretical Chemistry
dc.subject Organic Chemistry
dc.subject Inorganic Chemistry
dc.title Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.pmid 35682894
dc.identifier.doi https://doi.org/10.3390/ijms23116213
dc.relation.url http://www.scopus.com/inward/record.url?scp=85131705870&partnerID=8YFLogxK
dc.contributor.department Faculty of Medicine


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