Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig Exercise Intervention in Chronic Heart Failure and Aging catabolism study

Circulation. 2012 Jun 5;125(22):2716-27. doi: 10.1161/CIRCULATIONAHA.111.047381. Epub 2012 May 7.


Background: Muscle wasting occurs in both chronic heart failure (CHF) and normal aging and contributes to exercise intolerance and increased morbidity/mortality. However, the molecular mechanisms of muscle atrophy in CHF and their interaction with aging are still largely unknown. We therefore measured the activation of the ubiquitin-proteasome system and the lysosomal pathway of intracellular proteolysis in muscle biopsies of CHF patients and healthy controls in two age strata and assessed the age-dependent effects of a 4-week endurance training program on the catabolic-anabolic balance.

Methods and results: Sixty CHF patients (30 patients aged ≤55 years, mean age 46±5 years; 30 patients aged ≥65 years, mean age 72±5 years) and 60 healthy controls (30 subjects aged ≤55 years, mean age 50±5 years; 30 subjects aged ≥65 years, mean age 72±4 years) were randomized to 4 weeks of supervised endurance training or to a control group. Before and after the intervention, vastus lateralis muscle biopsies were obtained. The expressions of cathepsin-L and the muscle-specific E3 ligases MuRF-1 and MAFbx were measured by real-time polymerase chain reaction and confirmed by Western blot. At baseline, MuRF-1 expression was significantly higher in CHF patients versus healthy controls (mRNA: 624±59 versus 401±25 relative units; P=0.007). After 4 weeks of exercise training, MuRF-1 mRNA expression was reduced by -32.8% (P=0.02) in CHF patients aged ≤55 years and by -37.0% (P<0.05) in CHF patients aged ≥65 years.

Conclusions: MuRF-1, a component of the ubiquitin-proteasome system involved in muscle proteolysis, is increased in the skeletal muscle of patients with heart failure. Exercise training results in reduced MuRF-1 levels, suggesting that it blocks ubiquitin-proteasome system activation and does so in both younger and older CHF patients.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00176319.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / metabolism*
  • Biopsy
  • Cathepsin L / metabolism
  • Chronic Disease
  • Exercise / physiology*
  • Germany / epidemiology
  • Heart Failure / epidemiology
  • Heart Failure / metabolism*
  • Heart Failure / pathology
  • Humans
  • Middle Aged
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Physical Endurance / physiology*
  • Proteasome Endopeptidase Complex / metabolism
  • RNA, Messenger / metabolism
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Tripartite Motif Proteins
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism*


  • Muscle Proteins
  • RNA, Messenger
  • Tripartite Motif Proteins
  • Ubiquitin
  • FBXO32 protein, human
  • SKP Cullin F-Box Protein Ligases
  • TRIM63 protein, human
  • Ubiquitin-Protein Ligases
  • Cathepsin L
  • Proteasome Endopeptidase Complex

Associated data

  • ClinicalTrials.gov/NCT00176319