Abstract 19219: Differential Response of Murf-1 and Mafbx Expression in the Skeletal Muscle to Training Interventions in Heart Failure Patients
Introduction: Despite its prognostic implications the mechanisms of muscle wasting in chronic heart failure (CHF) are still incompletely understood. We have previously documented activation of the catabolic ubiquitin-proteasome system (UPS) with increased expression of Murf-1 in the skeletal muscle biopsies of CHF patients. However, it is unclear, if the second muscle specific E3-ligase MafBX is also involved in the wasting process and how Murf-1 and MafBX respond to endurance training in CHF patients of different age groups.
Methods: 60 CHF patients and 60 healthy subjects (HS) were randomized to 4 weeks of bicycle ergometer training at 70% of the heart rate reserve 4 × 20 min/day or to a control group (C). Before and after the intervention a spiroergometry, echocardiography, and a muscle biopsy of the vastus lateralis muscle were performed. Expression of the E3 ligases Murf-1 and MafBX was quantified by real-time PCR standardized for 18S-rRNA and Western blot.
Results: (1) Clinical Training Effects: In younger CHF patients (n= 15, age 45±3 years, BMI 26.8±2.7, LV-EF 26.8±2.6%) training improved V02 max by 36% from 13.3±1.6 to 18.1±1.5 mL/min kg (p=0.008 vs. control). In elderly CHF patients (n=15, age 68±4 years, BMI 25.3±2.9, LV-EF 27.4±3.0%) training increased V02 max by 33% from 12.9±1.4 to 17.1±1.1 mL/min kg (p=0.01 versus control). (2) Molecular Training Effects: At baseline Murf-1 mRNA expression in CHF patients was elevated versus HS at 624±59 versus 401±25 rel. units (p=0.007) and protein expression at 0.82±0.09 versus 0.57±0.04 rel. units (p=0.01). MafBX mRNA and protein expression did not differ in CHF patients and healthy subjects and did not change with age. Training was associated with a reduction of Murf-1 expression by 34.3% (p=0.02) in younger CHF patients and a reduction of 24.3% (p<0.05) in elderly. MafBX did not show any significant response to training.
Conclusions: Exercise training equally improves V02 max in younger and older patients with CHF. These clinical data underline the importance of exercise-based rehabilitation programs to prevent CHF related muscle wasting. On a molecular level, muscle wasting is mediated by selective activation of Murf-1 while MafBX levels remain unaffected by both CHF and the training intervention.
- © 2010 by American Heart Association, Inc.