Abstract 3198: Age-Dependency of Anti-Catabolic Effects of Exercise Training in the Skeletal Muscle of Patients With Chronic Heart Failure
Background: After the initial cardiac event leading to left ventricular dysfunction symptom progression and prognosis of chronic heart failure (CHF) are also related to secondary peripheral alterations such as skeletal muscle atrophy. However, the molecular basis of muscle wasting is still incompletely understood and pharmacological interventions are not yet available. We therefore analysed the activation of the proteolytic ubiquitin-proteasome pathway in the skeletal muscle of CHF patients and healthy subjects (HS) by measuring expression of a muscle specific E3-ligase (MuRF-1) and compared the response of MuRF-1 expression to a 4 week training program in old (>=65 years) and young (≤55 years) subjects.
Methods: A total of 50 CHF-patients and 55 HS were randomized to 4 weeks of ergometer training at 60 –70% of the heart rate reserve 4 times 20 min/day or to control. Before and after training a cardiopulmonary exercise test, and an echocardiogram were performed, and a skeletal muscle biopsy from the vastus lateralis muscle was obtained. We quantified MuRF-1 m-RNA expression by real-time PCR (standardized for 18S-rRNA) and protein expression by Western blot.
Results: After training in CHF patients (age 60.3±2.9 years, LV-EF 27.4±1.7%) VO2max increased from 14.9±3.3 to 18.1±4.7 ml/min/kg (p<0.01 versus control), and LV-EF from 26.8±4.6 to 33.1±5.5% (p=0.001 versus control). At baseline skeletal muscle MuRF-1 expression in CHF was significantly higher versus HS. After training MuRF-1 mRNA expression decreased by 26±8% and Murf-1 protein expression by 23±5% (both p<0.05 versus control). The relative reduction of MuRF-1 mRNA expression was more pronounced in patients >=65 years (−42.1±7.3%, mean age 68.0±3.8 years) as compared to those ≤55 years (−13.7±11.1%, p<0.05, mean age 45.0±3.4 years).
Conclusions: CHF is associated with activation of the catabolic ubiquitin-proteasome system in the skeletal muscle. Four weeks of ergometer training significantly reduced the elevated MuRF-1 expression by 26%. Surprisingly, the anticatabolic training effects were augmented among older CHF patients. These findings extend our current understanding of how physical activity readjusts the catabolic-anabolic balance in CHF in different age groups.