FIG 1.

Schematic representation of the systemic renin-angiotensin system. Renin converts angiotensinogen into angiotensin I (Ang I). Angiotensin-converting enzyme (ACE) converts Ang I into angiotensin II (Ang II), which binds to Ang II type 1 receptor (AT₁R), through which it exerts its harmful inflammatory effects. Angiotensin-converting enzyme 2 (ACE2) converts the majority of Ang II to Ang 1–7, which activates the Mas receptor (MasR) signaling pathway with protective downstream effects on the microcirculatory environment. Attachment of SARS-CoV-2 spike protein to ACE2 induces cleavage and release of the soluble form of ACE2 by ADAM-17, virus-receptor complex internalization and receptor downregulation. Reduced ACE2 expression is hypothesized to cause an imbalance between the classical ACE/Ang I/AT₁R and the protective ACE2/Ang 1–7/MasR axes that is central to the pathophysiology of coronavirus disease 2019 (COVID-19).