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

Area of Science:

• Biochemistry
• Trauma Medicine
• Systems Biology

Background:

• Shock-induced endotheliopathy (SHINE) negatively impacts trauma patient outcomes.
• Previous work identified four metabolic phenotypes in a small trauma cohort using endothelial cell (EC) metabolic profiling.
• Endothelial dysfunction is a critical factor in trauma-related morbidity and mortality.

Purpose of the Study:

• To identify and characterize distinct plasma metabolic phenotypes in a larger cohort of trauma patients.
• To investigate the association between these metabolic phenotypes and clinical outcomes, including injury severity and mortality.
• To infer endothelial cell (EC) metabolic patterns and their relationship to identified phenotypes.

Main Methods:

• Retrospective observational study of 99 trauma patients.
• Plasma metabolomic profiling using mass spectrometry on admission samples.
• Computational network analysis integrating quantified metabolites with a genome-scale metabolic model (iEC-GEM).

Main Results:

• Four distinct plasma metabolic phenotypes (A-D) were identified.
• Phenotype D correlated significantly with higher injury severity scores (p < 0.001).
• Phenotype D was prevalent in 91.6% of patients who died within 72 hours and showed impaired EC redox homeostasis compared to Phenotype A.

Conclusions:

• Trauma patients present with four identifiable plasma metabolic phenotypes upon admission.
• Phenotype D is strongly associated with increased mortality and severe injury.
• Impaired endothelial cell redox balance in Phenotype D may contribute to poor outcomes in trauma patients.