The Race for ACE: Targeting Angiotensin-Converting Enzymes (ACE) in SARS-CoV-2 Infection

Figure 1

Graphical illustration summarizing the canonical renin-angiotensin system cascade. In brief, prorenin is released by the kidney and activates via its prorenin-receptor proinflammatory pathways. Angiotensinogen as acute phase protein released from the liver is cleaved by renin to angiotensin I which is cleaved to the octapeptide angiotensin II (ANG II). In mast cells, this process uses an alternative pathway using the mast-cell chymase (orange). ANG II then activates via its G-protein coupled AT1-receptor proinflammatory pathways by stimulating the JAK-Stat signaling cascade as well as the phospholipase gamma signaling cascade (red). By stimulating its AT2-receptor, ANG II promotes the activation of predominantly anti-inflammatory pathways, i.e., cGMP, phospholipase A, or VEGF. ACE2 degrades ANG II to angiotensin 1-7 which in turn also stimulates regenerative pathways via the Mas receptor.