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 (LEICA) Catabolism Study
Background—Muscle wasting occurs both in chronic heart failure (CHF) and in 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 (UPS) Min muscle biopsies of CHF patients and healthy controls (HC) 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—60 CHF patients (30 patients≤55 years, mean age 46±5 years; 30 patients≥65 years, 72±5 years) and 60 healthy controls (HC, 30≤55 years, 50±5 years; 30≥65 years, 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 expression of cathepsin-L, the muscle-specific E3 ligases MuRF-1 and MAFbx were measured by real-time PCR and confirmed by Western blot. At baseline MuRF-1 expression was significantly higher in CHF patients versus HC (mRNA: 624±59 versus 401±25 rel. units; p=0.007). After four weeks of exercise training MuRF-1 mRNA expression was reduced by -32.8% (p=0.02) in CHF patients ≤55 years and by -37.0% (p<0.05) in CHF patients ≥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 UPS activation, and does so in both younger and older CHF patients.
Clinical Trial Registration Information—ClinicalTrials.gov; Identifier: NCT00176319.
- Received June 3, 2011.
- Accepted March 27, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited