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...
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doaj-1a07b945ff81451baed316c031233dfd2020-11-24T21:45:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9344910.1371/journal.pone.0093449ACE2 is augmented in dystrophic skeletal muscle and plays a role in decreasing associated fibrosis.Cecilia RiquelmeMaría José AcuñaJaviera TorrejónDaniela RebolledoDaniel CabreraRobson A SantosEnrique BrandanDuchenne 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.http://europepmc.org/articles/PMC3973684?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cecilia Riquelme María José Acuña Javiera Torrejón Daniela Rebolledo Daniel Cabrera Robson A Santos Enrique Brandan |
spellingShingle |
Cecilia Riquelme María José Acuña Javiera Torrejón Daniela Rebolledo Daniel Cabrera Robson A Santos Enrique Brandan ACE2 is augmented in dystrophic skeletal muscle and plays a role in decreasing associated fibrosis. PLoS ONE |
author_facet |
Cecilia Riquelme María José Acuña Javiera Torrejón Daniela Rebolledo Daniel Cabrera Robson A Santos Enrique Brandan |
author_sort |
Cecilia Riquelme |
title |
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_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_sort |
ace2 is augmented in dystrophic skeletal muscle and plays a role in decreasing associated fibrosis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
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. |
url |
http://europepmc.org/articles/PMC3973684?pdf=render |
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