The Renin-Angiotensin System: Going Beyond the Classical Paradigms

Robson A Souza Santos*, Gavin Y Oudit, Thiago Verano-Braga, Giovanni Canta, Ulrike Muscha Steckelings, Michael Bader

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Resumé

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.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology: Heart and Circulatory Physiology
Vol/bind316
Udgave nummer5
Sider (fra-til)H958-H970
ISSN0363-6135
DOI
StatusUdgivet - maj 2019

Fingeraftryk

Renin-Angiotensin System
Peptides
Angiotensin Receptors
Alanine
angiotensin I (1-7)
angiotensin converting enzyme 2

Citer dette

Santos, Robson A Souza ; Oudit, Gavin Y ; Verano-Braga, Thiago ; Canta, Giovanni ; Steckelings, Ulrike Muscha ; Bader, Michael. / The Renin-Angiotensin System : Going Beyond the Classical Paradigms. I: American Journal of Physiology: Heart and Circulatory Physiology. 2019 ; Bind 316, Nr. 5. s. H958-H970.
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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.",
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The Renin-Angiotensin System : Going Beyond the Classical Paradigms. / Santos, Robson A Souza; Oudit, Gavin Y; Verano-Braga, Thiago; Canta, Giovanni; Steckelings, Ulrike Muscha; Bader, Michael.

I: American Journal of Physiology: Heart and Circulatory Physiology, Bind 316, Nr. 5, 05.2019, s. H958-H970.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The Renin-Angiotensin System

T2 - Going Beyond the Classical Paradigms

AU - Santos, Robson A Souza

AU - Oudit, Gavin Y

AU - Verano-Braga, Thiago

AU - Canta, Giovanni

AU - Steckelings, Ulrike Muscha

AU - Bader, Michael

PY - 2019/5

Y1 - 2019/5

N2 - 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.

AB - 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.

KW - Alamandine

KW - Angiotensin-(1-7)

KW - Angiotensin-(1-9)

KW - Angiotensin-converting enzyme 2

KW - Heart failure

U2 - 10.1152/ajpheart.00723.2018

DO - 10.1152/ajpheart.00723.2018

M3 - Journal article

C2 - 30707614

VL - 316

SP - H958-H970

JO - American Journal of Physiology: Heart and Circulatory Physiology

JF - American Journal of Physiology: Heart and Circulatory Physiology

SN - 0363-6135

IS - 5

ER -