Abstract 1047: Anti-proteolytic Effects of Exercise Training in the Skeletal Muscle of Chronic Heart Failure Patients: Does Exercise Work Equally Well in All Age Groups?
Purpose: Muscle wasting in chronic heart failure (CHF) is an independent predictor of mortality. However, the molecular mechanisms that mediate muscle catabolism are largely unknown and no specific pharmacological agents are available to antagonize the loss of muscle mass. We therefore analysed two different protein degradation pathways in skeletal muscle biopsies of CHF patients and tested the age-dependent effects of exercise training to prevent muscle wasting.
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 ligase Murf-1 as part of the ubiquitin proteasome system was quantified by real-time PCR standardized for 18S-rRNA and Western blot. As a marker of lysosomal proteolysis cathepsin L was measured by real-time PCR.
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 VO2 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 VO2 max by 33% from 12.9±1.4 to 17.1±1.1 mL/min kg (p=0.01 versus control).
Molecular Training Effects: At baseline Murf-1 mRNA expression CHF patients was significantly elevated versus HS at 593±68 versus 410±27 rel. units (p=0.013) and protein expression at 0.90±0.08 versus 0.62±0.05 rel. units (p=0.018). Cathepsin L was not different between both groups.
Training induced 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. Cathepsin L expression remained unchanged.
Muscle wasting in CHF is mediated via the ubiquitin proteasome system and not the lysosomal system in the skeletal muscle.
Exercise training significantly improves VO2 max in both younger and older patients with CHF. These data underline the clinical role of exercise-based rehabilitation programs to prevent CHF related muscle wasting in the elderly.