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

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


Title: Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma
Author: Krocker, Joseph D.
Lee, Kyung Hyun
Henriksen, Hanne H.
Wang, Yao Wei Willa
Schoof, Erwin M.
Karvelsson, Sigurdur T.
Rolfsson, Óttar   orcid.org/0000-0003-4258-6057
Johansson, P. I.
Pedroza, Claudia
Wade, Charles E.
Date: 2022-06-01
Language: English
Scope:
Department: Faculty of Medicine
Series: International Journal of Molecular Sciences; 23(11)
ISSN: 1661-6596
DOI: https://doi.org/10.3390/ijms23116213
Subject: Coagulopathy; Complement; Damage-associated molecular patterns; Endothelium; Inflammation; Proteomics; Soluble thrombomodulin; Sympathetic; Syndecan-1; Trauma; Catalysis; Molecular Biology; Spectroscopy; Computer Science Applications; Physical and Theoretical Chemistry; Organic Chemistry; Inorganic Chemistry
URI: https://hdl.handle.net/20.500.11815/3894

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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

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.

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.

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