Abstract 16953: Effects of Exercise Training on PGC1α and Skeletal Muscle Function in Patients with Chronic Heart Failure - An Age-Stratified Study

Abstract

Introduction: Despite its prognostic implications the mechanisms of skeletal muscle wasting in chronic heart failure (CHF) are still not completely understood. We have previously documented a catabolic activation and reduction of mitochondria in skeletal muscle biopsies of CHF patients. PGC1α is a key regulator in both processes and it is unclear, if PGC1α can be positively altered by exercise training and if beneficial training effects are diminished in older patients. 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 x 20 min/day or to a control group (C). Before and after the intervention a spiroergometry, echocardiography, a force duration measurement and a muscle biopsy of the vastus lateralis muscle were performed. Expression of PGC1α 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 force duration from 31±3 to 45±4 seconds (p=0.004 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 force duration from 35±4 to 47±7 seconds (p=0.01 versus control). (2) Molecular Training Effects: At baseline PGC1α mRNA expression in CHF patients was reduced versus HS at 201±19 versus 401±25 rel. units (p=0.007) confirmed by a reduced protein expression at 0.22±0.09 in CHF patients versus 0.97±0.04 rel. units in HS (p=0.01). Exercise training was associated with an increase of PGC1α mRNA expression by 39.3% (p=0.02) in younger CHF patients and an increase of 34.7% (p<0.05) in the elderly. Conclusions: Exercise training equally improves skeletal muscle function 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, PGC1α is significantly increased on mRNA and protein level in both younger and older patients with CHF, implicating a reduced catabolic state and an improved oxidative capacity, both regulated by PGC1α.