Angiotensin-Converting Enzyme 2

Abstract

See related article, pages 729–736 There is a “new kid on the block” in the control of the renin-angiotensin system (RAS). The discovery of angiotensin (Ang)-converting enzyme (ACE)2, a catabolic enzyme, that cleaves the octapeptide, Ang II into a septapeptide, Ang-(1-7),1,2 has opened up new vistas in the way we think about the regulation and biological effects of Ang II. ACE 2 was originally discovered in yeast3 as a gene product that codes for a protein that is a homolog of the more widely known protease ACE. ACE2 cleaves the C-terminal amino acid from Ang II and other peptides. For many years, the work of Ferrario and Chappel4 provided evidence that Ang-(1-7) operated in the central nervous system, as well as in the peripheral circulation to produce effects that were, in general, opposite to that of Ang II. Recently, the discovery that Ang-(1-7) binds to a specific membrane receptor, the mas receptor,5–7 suggests that this metabolite may play a regulatory role in cell signaling and organ function. Clearly, the balance between the classic ACE and ACE2 will determine the physiological effect of activation of the RAS. Furthermore, the potential for therapeutic targeting of ACE2 and its role in the …