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

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Krocker, Joseph D ; Lee, Kyung Hyun ; Henriksen, Hanne H ; Wang, Yao-Wei Willa ; Schoof, Erwin M ; Karvelsson, Sigurdur T ; Rolfsson, Óttar ; Johansson, Pär I ; Pedroza, Claudia ; Wade, Charles E. / Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma. In: International Journal of Molecular Sciences. 2022 ; Vol. 23, No. 11.

Bibtex

@article{d5c6392463b74810bd987f43c8ec5efd,
title = "Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma",
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.",
keywords = "Biomarkers, Catecholamines, Humans, Inflammation, Prospective Studies, Proteome, Proteomics",
author = "Krocker, {Joseph D} and Lee, {Kyung Hyun} and Henriksen, {Hanne H} and Wang, {Yao-Wei Willa} and Schoof, {Erwin M} and Karvelsson, {Sigurdur T} and {\'O}ttar Rolfsson and Johansson, {P{\"a}r I} and Claudia Pedroza and Wade, {Charles E}",
year = "2022",
month = jun,
day = "1",
doi = "10.3390/ijms23116213",
language = "English",
volume = "23",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Molecular Diversity Preservation International (M D P I)",
number = "11",

}

RIS

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, Pär I

AU - Pedroza, Claudia

AU - Wade, Charles E

PY - 2022/6/1

Y1 - 2022/6/1

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 - Biomarkers

KW - Catecholamines

KW - Humans

KW - Inflammation

KW - Prospective Studies

KW - Proteome

KW - Proteomics

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

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 11

M1 - 6213

ER -

ID: 78750220