Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma
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Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma. / Krocker, Joseph D.; Lee, Kyung Hyun; Henriksen, Hanne H.; Wang, Yao Wei Willa; Schoof, Erwin M.; Karvelsson, Sigurdur T.; Rolfsson, Óttar; Johansson, P. I.; Pedroza, Claudia; Wade, Charles E.
In: International Journal of Molecular Sciences, Vol. 23, No. 11, 6213, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma
AU - Krocker, Joseph D.
AU - Lee, Kyung Hyun
AU - Henriksen, Hanne H.
AU - Wang, Yao Wei Willa
AU - Schoof, Erwin M.
AU - Karvelsson, Sigurdur T.
AU - Rolfsson, Óttar
AU - Johansson, P. I.
AU - Pedroza, Claudia
AU - Wade, Charles E.
N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Coagulopathy
KW - Complement
KW - Damage-associated molecular patterns
KW - Endothelium
KW - Inflammation
KW - Proteomics
KW - Soluble thrombomodulin
KW - Sympathetic
KW - Syndecan-1
KW - Trauma
UR - http://www.scopus.com/inward/record.url?scp=85131705870&partnerID=8YFLogxK
U2 - 10.3390/ijms23116213
DO - 10.3390/ijms23116213
M3 - Journal article
C2 - 35682894
AN - SCOPUS:85131705870
VL - 23
JO - International Journal of Molecular Sciences (Online)
JF - International Journal of Molecular Sciences (Online)
SN - 1661-6596
IS - 11
M1 - 6213
ER -
ID: 327071000