Angiotensina 1-7 restaura a força muscular de camundongos com distrofia muscular

Chile – a angiotensina 1-7 pertence ao sistema renina-angiotensina e tem efeito oposto ao da angiotensina II que é fibrosante através da TGF beta1. Neste estudo em camundongos com distrofia muscular o uso da angiotensina 1-7 dada por via oral reduziu a sinalização da TGF beta 1, reduziu a fibrose e o desaranjo muscular e aumentou a força muscular.

O resumo em inglês pode ser lido abaixo:

(Human Molecular Genetics, 2013) Restoration of muscle strength in dystrophic muscle by Angiotensin-1-7 through inhibition of TGF-β signaling

María José Acuña, Patrizia Pessina, Hugo Olguin, Daniel Cabrera, Carlos P. Vio, Michael Bader, Pura Muñoz-Canoves, Robson A. Santos, Claudio Cabello-Verrugio, and Enrique Brandan – Chile

Duchenne muscular dystrophy (DMD) is the most common inherited neuromuscular disease, and is characterized by the lack of dystrophin, muscle wasting, increased transforming growth factor (TGF)-β Smad dependent signaling and fibrosis. Acting via the Mas receptor, Angiotensin-1-7 (Ang-(1-7)) is part of the renin–angiotensin system, with the opposite effect to that of angiotensin II. We hypothesized that the Ang-(1-7)/Mas receptor axis might protects chronically damaged tissues as in skeletal muscle of the DMD mouse model mdx. Infusion or oral administration of Ang-(1-7) in mdx mice normalized skeletal muscle architecture, decreased local fibrosis and improved muscle function in vitro and in vivo. These positive effects were mediated by the inhibition of TGF-β Smad signaling, which in turn, led to reduction of the pro-fibrotic microRNA miR-21 concomitant with a reduction in the number of TCF4 expressing fibroblasts. Mdx mice infused with Mas antagonist (A-779) and mdx deficient for the Mas receptor showed highly deteriorated muscular architecture, increased fibrosis and TGF-β signaling with diminished muscle strength. These results suggest that this novel compound Ang-(1-7) might be used to improve quality of life and delay death in individuals with DMD and this drug should be investigated in further pre-clinical trials.