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Physiol Rev. 2018 Jan 1;98(1):505-553. doi: 10.1152/physrev.00023.2016.

The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7).

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National Institute of Science and Technology in Nanobiopharmaceutics, Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais , Belo Horizonte , Brazil ; Department of Biological Sciences, Federal University of Ouro Preto , Ouro Preto , Brazil ; Max-Delbrück-Center for Molecular Medicine (MDC), Berlin , Germany ; Berlin Institute of Health (BIH), Berlin , Germany ; Charité - University Medicine, Berlin , Germany ; DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin , Germany ; Institute for Biology, University of Lübeck , Lübeck , Germany.


The renin-angiotensin system (RAS) is a key player in the control of the cardiovascular system and hydroelectrolyte balance, with an influence on organs and functions throughout the body. The classical view of this system saw it as a sequence of many enzymatic steps that culminate in the production of a single biologically active metabolite, the octapeptide angiotensin (ANG) II, by the angiotensin converting enzyme (ACE). The past two decades have revealed new functions for some of the intermediate products, beyond their roles as substrates along the classical route. They may be processed in alternative ways by enzymes such as the ACE homolog ACE2. One effect is to establish a second axis through ACE2/ANG-(1-7)/MAS, whose end point is the metabolite ANG-(1-7). ACE2 and other enzymes can form ANG-(1-7) directly or indirectly from either the decapeptide ANG I or from ANG II. In many cases, this second axis appears to counteract or modulate the effects of the classical axis. ANG-(1-7) itself acts on the receptor MAS to influence a range of mechanisms in the heart, kidney, brain, and other tissues. This review highlights the current knowledge about the roles of ANG-(1-7) in physiology and disease, with particular emphasis on the brain.

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