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The renin-angiotensin system: going beyond the classical paradigms

Item Type:Review
Title:The renin-angiotensin system: going beyond the classical paradigms
Creators Name:Santos, R.A.S. and Oudit, G.Y. and Verano-Braga, T. and Canta, G. and Steckelings, U.M. and Bader, M.
Abstract:Thirty years ago a novel axis of the renin-angiotensin system (RAS) was unveiled by the discovery of angiotensin (Ang)-(1-7) generation in-vivo. Later angiotensin-converting enzyme 2 (ACE2) was shown to be the main mediator of this reaction and Mas was found to be the receptor for the heptapeptide. The functional analysis of this novel axis of the RAS which followed its discovery revealed numerous protective actions in particular for cardiovascular diseases. In parallel, similar protective actions were also described for one of the two receptors of Ang II, AT2R, in contrast to the other, AT1R, which mediates deleterious actions of this peptide e.g. in the setting of cardiovascular disease. Very recently, another branch of the RAS was discovered, based on Ang peptides in which the aminoterminal aspartate is replaced by alanine, the alatensins. Ala-Ang-(1-7) or alamandine was shown to interact with the Mas-related receptor (MrgD) and first functional data indicate that this peptide also exerts protective effects in the cardiovascular system. This review summarizes the presentations given at the International Union of Physiological Sciences Congress in Rio de Janeiro, 2017, during the symposium "The renin-angiotensin system: going beyond the classical paradigms", in which the signaling and the physiological actions of Ang-(1-7), ACE2, AT2R and the alatensins were reported (with a focus on non-CNS tissues) and the therapeutic opportunities based on these findings were discussed.
Keywords:Angiotensin-(1-7), Angiotensin-(1-9), Alamandine, Angiotensin Converting Enzyme 2, Heart Failure, Animals
Source:American Journal of Physiology Heart and Circulatory Physiology
ISSN:0363-6135
Publisher:American Physiological Society
Volume:316
Number:5
Page Range:H958-H970
Date:May 2019
Official Publication:https://doi.org/10.1152/ajpheart.00723.2018
PubMed:View item in PubMed

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