Faculty, Staff and Student Publications
Publication Date
6-1-2022
Journal
International Journal of Molecular Sciences
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, proteomics, trauma, syndecan-1, soluble thrombomodulin, endothelium, inflammation, sympathetic, damage-associated molecular patterns, complement, coagulopathy
DOI
10.3390/ijms23116213
PMID
35682894
PMCID
PMC9181752
PubMedCentral® Posted Date
6-1-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes