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. 2019 Mar 7;14(3):e0213096.
doi: 10.1371/journal.pone.0213096. eCollection 2019.

Circulating angiotensin peptides levels in Acute Respiratory Distress Syndrome correlate with clinical outcomes: A pilot study

Raju Reddy  1 , Isaac Asante  2 , Siyu Liu  2 , Pranay Parikh  1 , Janice Liebler  1 , Zea Borok  1   3 , Kathleen Rodgers  2 , Ahmet Baydur  1 , Stan G Louie  2
Affiliations

Circulating angiotensin peptides levels in Acute Respiratory Distress Syndrome correlate with clinical outcomes: A pilot study

Raju Reddy et al. PLoS One. .

Abstract

Rationale: We propose renin angiotensin system (RAS) peptides are critical in wound reparative processes such as in acute respiratory distress syndrome (ARDS). Their role in predicting clinical outcomes in ARDS has been unexplored; thus, we used a targeted metabolomics approach to investigate them as potential predictors of outcomes.

Methods: Thirty-nine ARDS patients were enrolled within 24 hours of ARDS diagnosis. Plasma RAS peptide levels were quantified at study entry and 24, 48 and 72 hours using a liquid chromatography-mass spectrometry based metabolomics assay. RAS peptide concentrations were compared between survivors and non-survivors, and were correlated with clinical and pulmonary measures.

Measurements and main results: Angiotensin I (Ang-I or A(1-10)) levels were significantly higher in non-survivors at study entry and 72 hours. ARDS survival was associated with lower A(1-10) concentration (OR 0.36, 95% CI 0.18-0.72, p = 0.004) but higher A(1-9) concentration (OR 2.24, 95% CI 1.15-4.39, p = 0.018), a biologically active metabolite of A(1-10) and an agonist of angiotensin II receptor type 2. Survivors had significantly higher median A(1-9)/A(1-10) and A(1-7)/A(1-10) ratios than the non-survivors (p = 0.001). Increased A(1-9)/A(1-10) ratio suggests that angiotensin converting enzyme II (ACE2) activity is higher in patients who survived their ARDS insult while an increase in A(1-7)/A(1-10) ratio suggests that ACE activity is also higher in survivors.

Conclusion: A(1-10) accumulation and reduced A(1-9) concentration in the non-survivor group suggest that ACE2 activities may be reduced in patients succumbing to ARDS. Plasma levels of both A(1-10) and A(1-9) and their ratio may serve as useful biomarkers for prognosis in ARDS patients.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Metabolic pathway of angiotensinogen.
This figure shows the major metabolites of angiotensinogen, the receptors they act on and the associated enzymes. AT4 is insulin regulated membrane aminopeptidase (IRAP).
See this image and copyright information in PMC

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