Angiotensin-(1-7) decreases skeletal muscle atrophy induced by angiotensin II through a Mas receptor-dependent mechanism

Franco Cisternas, María Gabriela Morales, Carla Meneses, Felipe Simon, Enrique Brandan, Johanna Abrigo, Yaneisi Vazquez, Claudio Cabello-Verrugio

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

Skeletal muscle atrophy is a pathological condition characterized by the loss of strength and muscle mass, an increase in myosin heavy chain (MHC) degradation and increase in the expression of two muscle-specific ubiquitin ligases: atrogin-1 and MuRF-1. Angiotensin II (AngII) induces muscle atrophy. Angiotensin-(1-7) [Ang-(1-7)], through its receptor Mas, produces the opposite effects than AngII. We assessed the effects of Ang-(1-7) on the skeletal muscle atrophy induced by AngII. Our results show that Ang-(1-7), through Mas, prevents the effects induced by AngII in muscle gastrocnemius: the decrease in the fibre diameter, muscle strength and MHC levels and the increase in atrogin-1 and MuRF-1. Ang-(1-7) also induces AKT phosphorylation. In addition, our analysis in vitro using C2C12 myotubes shows that Ang-(1-7), through a mechanism dependent on Mas, prevents the decrease in the levels of MHC and the increase in the expression of the atrogin-1 and MuRF-1, both induced by AngII. Ang-(1-7) induces AKT phosphorylation in myotubes; additionally, we demonstrated that the inhibition of AKT with MK-2206 decreases the anti-atrophic effects of Ang-(1-7). Thus, we demonstrate for the first time that Ang-(1-7) counteracts the skeletal muscle atrophy induced by AngII through a mechanism dependent on the Mas receptor, which involves AKT activity. Our study indicates that Ang-(1-7) is novel molecule with a potential therapeutical use to improve muscle wasting associated, at least, with pathologies that present high levels of AngII.

Original languageEnglish
Pages (from-to)307-319
Number of pages13
JournalClinical Science
Volume128
Issue number5
DOIs
Publication statusPublished - 2015

Keywords

  • Angiotensin-(1-7)
  • Atrophy
  • Mas
  • Muscle wasting
  • Skeletal muscle

ASJC Scopus subject areas

  • Medicine(all)

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