5.2 Rebalancing the RAAS axes by rhACE2
SARS-CoV-2 infection reduced ACE2 activity and increased the receptor
consumption, further exacerbating pathophysiological changes, such as
ACE/ACE2 ratio imbalance. Accordingly, there are several potential
approaches to address ACE2-mediated COVID-19, including increases the
expression and the activity of ACE2 to regulate the imbalance of RAAS.
The imbalance of RAAS may result in abnormal high blood pressure and
further induce multiple organ damage. Activation of the ACE2/Ang
(1-7)/MasR signaling pathway or inhibition of the ACE/Ang Ⅱ/AT1R pathway
may be alternative treatments for novel coronavirus. Treatment with
rhACE2 is the direct approach to regulate the ACE2/Ang (1-7)/MasR axis.
A few pilot clinical studies have been conducted using rhACE2 in ARDS,
and sepsis. For example, Monteil found that clinical grade recombinant
human soluble ACE2 can significantly block early stages of SARS-CoV-2
infections(Monteil et al. , 2020). In a pilot clinical trial
(NCT01597635)(Khan et al. , 2017), patients with ARDS treated with
rhACE2 exhibited decreased plasma Ang Ⅱ and elevated plasma Ang (1-7).
An additional pilot study (NCT101884051) investigated the effects of
rhACE2 in pulmonary arterial hypertension which is found that the ACE2
activity reduced(Hemnes et al. , 2018). The pharmacokinetics and
pharmacodynamics of soluble rhACE2 treatment in healthy volunteers
showed increased Ang (1-7) with no effect on blood pressure and heart
rate (NCT00886353)(Haschke et al. , 2013). These clinical trials
showed treatment with rhACE2 may improve excessive inflammation via
activation of the ACE2/Ang (1-7)/Mas signaling pathway. Interestingly,
treatment with rhACE2 may be completed with SARS-Cov-2 for ACE2, thus
reduced the susceptibility of ACE2 binding to the virus.