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

Joseph D. Krocker*, Kyung Hyun Lee, Hanne H. Henriksen, Yao-Wei Willa Wang, Erwin M. Schoof, Sigurdur T. Karvelsson, Óttar Rolfsson, Pär I. Johansson, Claudia Pedroza, Charles E. Wade

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

3 Downloads (Pure)

Abstract

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. 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. 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. 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.
Original languageEnglish
Article number6213
JournalInternational Journal of Molecular Sciences
Volume23
Issue number11
Number of pages26
ISSN1661-6596
DOIs
Publication statusPublished - 2022

Keywords

  • Proteomics
  • Trauma
  • Syndecan-1
  • Soluble thrombomodulin
  • Endothelium
  • Inflammation
  • Sympathetic
  • Damage-associated molecular patterns
  • Complement
  • Coagulopathy

Fingerprint

Dive into the research topics of 'Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma'. Together they form a unique fingerprint.

Cite this