Figure 1: Overview of the Renin-Angiotensin-System.

Overview of the Renin–Angiotensin-System including its peptides (blue), enzymes (green), receptors (purple) and targets for therapeutic interventions (red). Starting from Angiotensinogen as the substrate, Renin is a main enzyme to generate downstream angiotensin peptides. The classical arm of the RAS includes Angiotensin II, which is synthesized from Angiotensin I by Angiotensin Converting Enzyme (ACE) and exerts its effects by activating the Angiotensin II receptor type 1 (AT₁). While Angiotensin II is the main effector peptide, multiple other Angiotensin II-degrading and Angiotensin II-independent pathways exist including a variety of angiotensin peptides and enzymes like Angiotensin Converting Enzyme 2 (ACE2), Neprilysin (NEP), Chymase, Prolylendopeptidase (PEP), Prolylcarboxypeptidase (PRCP), Aminopeptidase A (APA) and Aminopeptidase N (APN). Apart from the AT₁ receptor, alternative receptors of RAS peptides include the Angiotensin II receptors typ 2 and 4 (AT₂ and AT₄) as well as the MAS receptor activated by Angiotensin 1–7. Therapeutic interventions targeted at Angiotensin II may inhibit upstream enzymes like Renin and ACE or block the AT₁ receptor as the main receptor of Angiotensin II. Recombinant ACE2 may enhance the degradation of Angiotensin II and its precursor Angiotensin I thereby reducing the levels of Angiotensin II and balancing its effects on Renin-Angiotensin-System. Created with biorender.com