Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients

Hanne H. Henriksen, Igor Marín de Mas, Lars K. Nielsen, Joseph Krocker, Jakob Stensballe, Sigurður T. Karvelsson, Niels H. Secher, Óttar Rolfsson, Charles E. Wade, Pär I. Johansson*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

In trauma patients, shock-induced endotheliopathy (SHINE) is associated with a poor prognosis. We have previously identified four metabolic phenotypes in a small cohort of trauma patients (N = 20) and displayed the intracellular metabolic profile of the endothelial cell by integrating quantified plasma metabolomic profiles into a genome-scale metabolic model (iEC-GEM). A retrospective observational study of 99 trauma patients admitted to a Level 1 Trauma Center. Mass spectrometry was conducted on admission samples of plasma metabolites. Quantified metabolites were analyzed by computational network analysis of the iEC-GEM. Four plasma metabolic phenotypes (A–D) were identified, of which phenotype D was associated with an increased injury severity score (p < 0.001); 90% (91.6%) of the patients who died within 72 h possessed this phenotype. The inferred EC metabolic patterns were found to be different between phenotype A and D. Phenotype D was unable to maintain adequate redox homeostasis. We confirm that trauma patients presented four metabolic phenotypes at admission. Phenotype D was associated with increased mortality. Different EC metabolic patterns were identified between phenotypes A and D, and the inability to maintain adequate redox balance may be linked to the high mortality.

Original languageEnglish
Article number2257
JournalInternational Journal of Molecular Sciences
Volume24
Issue number3
ISSN1661-6596
DOIs
Publication statusPublished - 2023

Keywords

  • Endotheliopathy
  • Genome-scale metabolic model
  • Metabolomics
  • Systems biology
  • Trauma
  • Tricarboxylic acid cycle

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