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Oleic Acid-Injection in Pigs As a Model for Acute Respiratory Distress Syndrome
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Differential Protein Expression among Two Different Ovine ARDS Phenotypes-A Preclinical Randomized Study.

Karin Wildi1,2,3, Mahe Bouquet1,2, Carmen Ainola1,2

  • 1Critical Care Research Group, The Prince Charles Hospital, Brisbane 4032, Australia.

Metabolites
|July 27, 2022
PubMed
Summary

Researchers identified a 33-protein signature to distinguish between two Acute Respiratory Distress Syndrome (ARDS) phenotypes in sheep models. This discovery aids in understanding ARDS protein expression patterns and potential therapeutic targets.

Keywords:
Acute Respiratory Distress Syndrome (ARDS)SWATHovine modelphenotypesprotein expression profiles

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Area of Science:

  • Proteomics
  • Animal Models
  • Critical Care Medicine

Background:

  • Acute Respiratory Distress Syndrome (ARDS) presents significant global mortality and morbidity.
  • Inflammatory subphenotypes offer novel avenues for ARDS research.
  • Ovine models provide a translational platform for studying ARDS.

Purpose of the Study:

  • To characterize and compare protein expression profiles in two distinct ovine ARDS lung injury models.
  • To identify a protein signature that differentiates between ARDS phenotypes.
  • To explore temporal protein expression changes in response to ARDS induction.

Main Methods:

  • Two ovine ARDS models were utilized, including one with endotoxin infusion (phenotype 2).
  • Nine mechanically ventilated animals were allocated to phenotype 1 (n=5) or phenotype 2 (n=4).
  • Data-independent SWATH-MS was employed for comprehensive plasma protein abundance analysis at multiple time points (baseline, 2, 6, 12, 24 h).

Main Results:

  • Cluster analysis indicated that protein patterns evolved more significantly over time than due to differing ARDS models.
  • A distinct protein signature of 33 proteins demonstrated high accuracy in differentiating between phenotype 1 and phenotype 2.
  • Network analysis revealed time-dependent activation of proteins involved in inflammation, defense, complement and coagulation, oxygen binding, and lipid metabolism.
  • Five specific proteins (LUM, CA2, KNG1, AGT, IGJ) showed increased expression in phenotype 2.

Conclusions:

  • Time is a more significant factor than the specific ARDS model in shaping protein expression patterns.
  • A 33-protein signature accurately distinguishes between the studied ARDS phenotypes.
  • Activated pathways include inflammation, defense, complement/coagulation, and lipid metabolism, offering potential targets for ARDS management.