Figure 1.

Expression of angiotensin-converting enzyme 2 (ACE2) in human tissues and organs, its counter-regulatory effects on the ACE → Ang II → AT₁ axis and interaction with coronavirus disease 2019 (COVID-19). ACE2 is ubiquitous and widely expressed in many organs targeted and damaged by COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is a membrane-bound enzyme and an endogenous counter-regulator of the renin-angiotensin hormonal cascade. It degrades angiotensin II (Ang II) to angiotensin 1-7 (Ang 1-7) that exerts beneficial effects opposed to those of Ang II. Ang 1-7 acts through the G protein-coupled receptor MAS and, to a lesser extent, Ang II type 2 receptors (AT₂). ACE and ACE2 and their major products, Ang II and Ang 1-7, respectively, are linked in almost a ying/yang process, that is, when one decreases, the other increases and vice versa [18]. Thus, reduced activity of the deleterious ACE → Ang II → Ang II receptor type 1 (AT₁) axis (red) is coupled with increased activity of the protective ACE2 → Ang 1-7 → MAS receptor axis (green). A lower ACE/ACE2 ratio (A) (occurring in women, in exercise-trained individuals and patients well-treated with ACE inhibitors (ACE-I)) leads to beneficial effects such as vasorelaxation, anti-inflammatory, anti-oxidative, anti-fibrotic and anti-thrombotic effects that predispose towards a lower risk of cardiovascular disease (CVD) and better COVID-19 outcomes. By contrast, a high ACE/ACE2 ratio (B) that is increased in males, elderly and many pathologies (especially CVD, pulmonary and renal diseases and obesity) may aggravate COVID-19 infection [19,20,21,22].