Maybe some thoughts on this study?
Circulating angiotensin peptides levels in Acute Respiratory Distress Syndrome correlate with clinical outcomes: A pilot study
To date, no study has used the metabolomics approach to determine circulating levels of RAS peptides as predictors of survival outcomes in ARDS. Using this approach, we found that plasma A(1–10) levels were predictive for clinical outcome at study entry. Although a statistically significant difference was also achieved at 72 hours, we avoided possible bias arising from deaths in one of the groups by focusing on the predictive capacity using RAS peptides at study entry. No statistically significant differences were found in plasma levels of A(1–8) and A(1–7) between the two groups at any time point. However, upon analyzing peptide ratios (product/reactant), there were suggested differences in the two groups’ comparative ability to form the active RAS metabolites.
To determine whether higher levels of A(1–10) amongst non-survivors is a consequence of increased biosynthesis or reduced metabolism, we examined levels of both precursor peptides and downstream metabolic peptides. A(1–12) was used as a surrogate marker for angiotensinogen. There was no difference in A(1–12) between the two outcomes group, suggesting that higher levels of A(1–10) in the non-survivor group were not likely due to its increased synthesis. Furthermore, levels of downstream products such as A(1–9), A(1–8) and A(1–7) were lower in the non-survivor group, but not statistically different. Despite the lack of statistical significance, survivors had approximately three times higher median plasma A(1–7) levels suggesting the metabolism to form bioactive peptides may be impeded. Taken together, these findings suggest that non-survivors have reduced metabolism of A(1–10) which could be due to reduction in ACE and/or ACE2 enzymatic activities as a consequence of more severe lung endothelial and epithelial injuries in the non-survivor group.
Cell-associated ACE has significantly higher catalytic activity as compared to circulating ACE . Patients with severe ARDS may sustain more lung injury to the endothelium and epithelium thus reducing the levels of cell-associated enzymes which corresponded with increased SOFA scores and lactate serum levels. Other evidence supporting decreased enzymatic activity in the non-survivor group may be inferred by comparing peptide ratios (product/reactant) between the two groups. Survivors had higher levels of downstream products as suggested by higher peptide ratios of A(1–10)/A(1–12), A(1–8)/A(1–10), A(1–7)/A(1–9) and A(1–7)/A(1–8). The small sample size may account for why median levels of some peptide ratios such as A(1–7)/A(1–9) and A(1–7)/A(1–8) were not significantly different between survival and non-survival groups. Reduction in ACE and ACE2 enzymatic activity may ultimately lead to accumulation of A(1–10) in patients who succumb to ARDS. Therefore, elevated levels of A(1–10) at study initiation may serve as a useful marker to predict non-survival amongst ARDS patient