Abstract 3963: Anabolic Effects of Regular Exercise Training: Correlation between Ubiquitin-Protein Ligase MURF-1 Expression and Skeletal Muscle Size in Patients with Severe Chronic Heart Failure
In advanced chronic heart failure (CHF), exercise capacity is severely impaired due to ultrastructural alterations of the skeletal muscle finally leading to atrophy. It has been suggested that an upregulation of E3-ligase MURF-1 expression, which consequently leads to an activation of the ubiquitin-proteasome pathway, is involved in the process of muscle proteolysis. Aim of this trial was to investigate, whether exercise training-mediated changes in expression of MURF-1 contribute to an increase in skeletal muscle size (CSA) and exercise capacity in pts. with end-stage CHF fulfilling the inclusion criteria of the COPERNICUS trial.
Methods: Twenty-eight patients (pts) with end-stage CHF (LVEF 24±2 %, NYHA class IIIb) were randomized to 12 weeks (wks) of exercise training (50 – 60% of peak oxygen uptake, 30 minutes daily on a bicycle ergometer) or sedentary lifestyle (control, C). At baseline (B) and after 12 wks, a symptom-limited spiroergometry was performed, percutaneous biopsies of the vastus lateralis muscle were obtained and expression of MURF-1 was determined by RT-PCR. Skeletal muscle cross sectional area (CSA) at mid femur level was measured by CT scans.
Results: Exercise training decreased expression of MURF-1 by -47±7% (p<0.05 vs. B, C). This was associated with an increase in muscle CSA by +9% (from 132±4 cm2 to 144±8 cm2, p<0.05 vs. B, C). The decline in Murf-1 expression was clearly linked to the increase in muscle CSA (r=0.62, p<0.05) in the training group. Additionally, maximal oxygen consumption as a read out of exercise capacity was found to be significantly augmented by +16.6% after 12 wks of exercise training (from 15.3±3.3 to 17.8±3.2, p<0.05 vs. B,C). All of the above-mentioned parameters remained virtually unchanged during the study period in the control group.
Conclusion: The increase in skeletal muscle size as a result of the training intervention might be partially the result of a down-regulation in MURF-1 expression and hence a blunted activation of the ubiquitin-proteasome pathway. This might favour endogenous muscle regeneration in end-stage CHF by readjusting the balance between anabolic and catabolic processes.