Fig. 1

The renin-angiotensin system (RAS) is organized into two opposite arms that must be properly balanced: a pro-oxidative/pro-inflammatory axis (in red), mainly formed by Angiotensin II that binds AT1 receptors (AT1R), and an antioxidative/anti-inflammatory axis (in green), mainly formed by Angiotensin II-binding AT2 receptors and Angiotensin 1–7-binding Mas receptors (MasR) or Mas-related G protein-coupled receptors. The enzyme prorenin/renin acting on the precursor protein angiotensinogen produces Angiotensin I, which is converted to Angiotensin II by the angiotensin-converting enzyme (ACE or ACE1). Renin and its precursor prorenin (PR) can also bind specific pro-oxidative PR receptors (PRR). Angiotensin-converting enzyme 2 (ACE2; also known as the major entry receptor for the SARS-COV viruses) plays a major role in balancing both RAS arms, as ACE2 (together with other peptidases such as Neprilysin, NEP) transforms peptides of the pro-inflammatory axis (Angiotensin I and, particularly, Angiotensin II) into peptides of the anti-inflammatory axis (Angiotensin 1–9 and, particularly Angiotensin 1–7)