Serum levels of ACE and Ang II are elevated in patients with ARDS and sepsis (55,56). Studies focused on microvascular dysfunction in sepsis showed that the degree of elevation in plasma renin and Ang II were correlated with the extent of organ failure and the degree of microvascular dysfunction, especially in patients who received exogenous vasoconstrictors (56); there was also a negative correlation between re-oxygenation rates and both concentrations of plasma renin and Ang II (56). In a pilot clinical trial (Safety, Tolerability, PK and PD of GSK2586881 in Patients With Acute Lung Injury; NCT01597635), patients with ARDS who were treated with rhACE2 exhibited decreased plasma Ang II and elevated plasma Ang 1-7 and surfactant protein-D, which is involved in innate immunity (57). IL-6 concentrations in treated patients were also reduced, albeit statistically insignificantly, which was due to intrasubject variability and baseline imbalance. Although rhACE2 attenuated RAS mediators, infusions of the medication did not show improvement in physiological or clinical measures of ARDs in this study (57).