Impact of angiotensin II on skeletal muscle metabolism and function in mice: Contribution of IGF-1, Sirtuin-1 and PGC-1α

Katharina Kackstein, Andrej Teren, Yasuharu Matsumoto, Norman Mangner, Sven Möbius-Winkler, Axel Linke, Gerhard Schuler, Karla Punkt, Volker Adams

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Activation of the renin-angiotensin-aldosterone system and increased levels of angiotensin II (Ang-II) occurs in numerous cardiovascular diseases such as chronic heart failure (CHF). Another hallmark in CHF is a reduced exercise tolerance with impaired skeletal muscle function. The aim of this study was to investigate in an animal model the impact of Ang-II on skeletal muscle function and concomitant molecular alterations. Mice were infused with Ang-II for 4 weeks. Subsequently, skeletal muscle function of the soleus muscle was assessed. Expression of selected proteins was quantified by qRT-PCR and Western blot. Infusion of Ang-II resulted in a 33% reduction of contractile force, despite a lack of changes in muscle weight. At the molecular level an increased expression of NAD(P)H oxidase and a reduced expression of Sirt1, PGC-1α and IGF-1 were noticed. No change was evident for the ubiquitin E3-ligases MuRF1 and MafBx and α-sarcomeric actin expression. Cytophotometrical analysis of the soleus muscle revealed a metabolic shift toward a glycolytic profile. This study provides direct evidence of Ang-II-mediated, metabolic deterioration of skeletal muscle function despite preserved muscle mass. One may speculate that the Ang-II-mediated loss of muscle force is due to an activation of NAD(P)H oxidase expression and a subsequent ROS-induced down regulation of IGF-1, PGC-1α and Sirt1.

Original languageEnglish
Pages (from-to)363-370
Number of pages8
JournalActa Histochemica
Volume115
Issue number4
DOIs
Publication statusPublished - 2013 May

Keywords

  • Angiotensin II
  • Mice
  • Muscle atrophy
  • Renin-angiotensin-aldosterone system
  • Skeletal muscle
  • Soleus muscle

ASJC Scopus subject areas

  • Histology
  • Cell Biology

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