Cargando…
ACE2 Is Augmented in Dystrophic Skeletal Muscle and Plays a Role in Decreasing Associated Fibrosis
Duchenne muscular dystrophy (DMD) is the most common inherited neuromuscular disease and is characterized by absence of the cytoskeletal protein dystrophin, muscle wasting, and fibrosis. We previously demonstrated that systemic infusion or oral administration of angiotensin-(1-7) (Ang-(1-7)), a pept...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973684/ https://www.ncbi.nlm.nih.gov/pubmed/24695436 http://dx.doi.org/10.1371/journal.pone.0093449 |
_version_ | 1782479358881955840 |
---|---|
author | Riquelme, Cecilia Acuña, María José Torrejón, Javiera Rebolledo, Daniela Cabrera, Daniel Santos, Robson A. Brandan, Enrique |
author_facet | Riquelme, Cecilia Acuña, María José Torrejón, Javiera Rebolledo, Daniela Cabrera, Daniel Santos, Robson A. Brandan, Enrique |
author_sort | Riquelme, Cecilia |
collection | PubMed |
description | Duchenne muscular dystrophy (DMD) is the most common inherited neuromuscular disease and is characterized by absence of the cytoskeletal protein dystrophin, muscle wasting, and fibrosis. We previously demonstrated that systemic infusion or oral administration of angiotensin-(1-7) (Ang-(1-7)), a peptide with opposing effects to angiotensin II, normalized skeletal muscle architecture, decreased local fibrosis, and improved muscle function in mdx mice, a dystrophic model for DMD. In this study, we investigated the presence, activity, and localization of ACE2, the enzyme responsible for Ang-(1-7) production, in wild type (wt) and mdx skeletal muscle and in a model of induced chronic damage in wt mice. All dystrophic muscles studied showed higher ACE2 activity than wt muscle. Immunolocalization studies indicated that ACE2 was localized mainly at the sarcolemma and, to a lesser extent, associated with interstitial cells. Similar results were observed in the model of chronic damage in the tibialis anterior (TA) muscle. Furthermore, we evaluated the effect of ACE2 overexpression in mdx TA muscle using an adenovirus containing human ACE2 sequence and showed that expression of ACE2 reduced the fibrosis associated with TA dystrophic muscles. Moreover, we observed fewer inflammatory cells infiltrating the mdx muscle. Finally, mdx gastrocnemius muscles from mice infused with Ang-(1-7), which decreases fibrosis, contain less ACE2 associated with the muscle. This is the first evidence supporting ACE2 as an important therapeutic target to improve the dystrophic skeletal muscle phenotype. |
format | Online Article Text |
id | pubmed-3973684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39736842014-04-04 ACE2 Is Augmented in Dystrophic Skeletal Muscle and Plays a Role in Decreasing Associated Fibrosis Riquelme, Cecilia Acuña, María José Torrejón, Javiera Rebolledo, Daniela Cabrera, Daniel Santos, Robson A. Brandan, Enrique PLoS One Research Article Duchenne muscular dystrophy (DMD) is the most common inherited neuromuscular disease and is characterized by absence of the cytoskeletal protein dystrophin, muscle wasting, and fibrosis. We previously demonstrated that systemic infusion or oral administration of angiotensin-(1-7) (Ang-(1-7)), a peptide with opposing effects to angiotensin II, normalized skeletal muscle architecture, decreased local fibrosis, and improved muscle function in mdx mice, a dystrophic model for DMD. In this study, we investigated the presence, activity, and localization of ACE2, the enzyme responsible for Ang-(1-7) production, in wild type (wt) and mdx skeletal muscle and in a model of induced chronic damage in wt mice. All dystrophic muscles studied showed higher ACE2 activity than wt muscle. Immunolocalization studies indicated that ACE2 was localized mainly at the sarcolemma and, to a lesser extent, associated with interstitial cells. Similar results were observed in the model of chronic damage in the tibialis anterior (TA) muscle. Furthermore, we evaluated the effect of ACE2 overexpression in mdx TA muscle using an adenovirus containing human ACE2 sequence and showed that expression of ACE2 reduced the fibrosis associated with TA dystrophic muscles. Moreover, we observed fewer inflammatory cells infiltrating the mdx muscle. Finally, mdx gastrocnemius muscles from mice infused with Ang-(1-7), which decreases fibrosis, contain less ACE2 associated with the muscle. This is the first evidence supporting ACE2 as an important therapeutic target to improve the dystrophic skeletal muscle phenotype. Public Library of Science 2014-04-02 /pmc/articles/PMC3973684/ /pubmed/24695436 http://dx.doi.org/10.1371/journal.pone.0093449 Text en © 2014 Riquelme et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Riquelme, Cecilia Acuña, María José Torrejón, Javiera Rebolledo, Daniela Cabrera, Daniel Santos, Robson A. Brandan, Enrique ACE2 Is Augmented in Dystrophic Skeletal Muscle and Plays a Role in Decreasing Associated Fibrosis |
title | ACE2 Is Augmented in Dystrophic Skeletal Muscle and Plays a Role in Decreasing Associated Fibrosis |
title_full | ACE2 Is Augmented in Dystrophic Skeletal Muscle and Plays a Role in Decreasing Associated Fibrosis |
title_fullStr | ACE2 Is Augmented in Dystrophic Skeletal Muscle and Plays a Role in Decreasing Associated Fibrosis |
title_full_unstemmed | ACE2 Is Augmented in Dystrophic Skeletal Muscle and Plays a Role in Decreasing Associated Fibrosis |
title_short | ACE2 Is Augmented in Dystrophic Skeletal Muscle and Plays a Role in Decreasing Associated Fibrosis |
title_sort | ace2 is augmented in dystrophic skeletal muscle and plays a role in decreasing associated fibrosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973684/ https://www.ncbi.nlm.nih.gov/pubmed/24695436 http://dx.doi.org/10.1371/journal.pone.0093449 |
work_keys_str_mv | AT riquelmececilia ace2isaugmentedindystrophicskeletalmuscleandplaysaroleindecreasingassociatedfibrosis AT acunamariajose ace2isaugmentedindystrophicskeletalmuscleandplaysaroleindecreasingassociatedfibrosis AT torrejonjaviera ace2isaugmentedindystrophicskeletalmuscleandplaysaroleindecreasingassociatedfibrosis AT rebolledodaniela ace2isaugmentedindystrophicskeletalmuscleandplaysaroleindecreasingassociatedfibrosis AT cabreradaniel ace2isaugmentedindystrophicskeletalmuscleandplaysaroleindecreasingassociatedfibrosis AT santosrobsona ace2isaugmentedindystrophicskeletalmuscleandplaysaroleindecreasingassociatedfibrosis AT brandanenrique ace2isaugmentedindystrophicskeletalmuscleandplaysaroleindecreasingassociatedfibrosis |