ACE2, a new regulator of the renin-angiotensin system

Abstract

Angiotensin-converting enzyme (ACE) is a zinc metalloproteinase and a key regulator of the renin-angiotensin system (RAS). ACE2 is a newly described enzyme identified in rodents and humans with a more restricted distribution than ACE, and is found mainly in heart and kidney. ACE2 cleaves a single residue from angiotensin I (Ang I) to generate Ang 1-9, and degrades Ang II, the main effector of the RAS, to the vasodilator Ang 1-7. The importance of ACE2 in normal physiology and pathophysiological states is largely unknown. ACE2 might act in a counter-regulatory manner to ACE, modulating the balance between vasoconstrictors and vasodilators within the heart and kidney, and playing a significant role in regulating cardiovascular and renal function.

Figure 1

The renin–angiotensin system (RAS) pathway. Schematic diagram of the classical RAS (left), showing the main pathway for angiotensin II (Ang II) generation from Ang I via angiotensin-converting enzyme (ACE). In the classical view, Ang II mediates all known effects via the AT1 receptor. On the right is the updated view of the RAS, showing the role of ACE2 in degrading Ang I to Ang 1–9, and Ang II to the vasodilator Ang 1–7. In this version of the RAS, Ang II also mediates effects via the G-protein-coupled AT2 receptor, whereas Ang 1–7 acts through the Mas receptor.