Abstract 3955: Anti-Catabolic Peripheral Effects of a 4-Week Endurance Training Program in Patients with Stable Chronic Heart Failure and Healthy Subjects: Reduced Rnf28 Expression in Skeletal Muscle Biopsies of Trained Subjects.
Background: Protein catabolism via the ubiquitin-proteasome pathway is regulated by tagging structural proteins with organ-specific E3-ligases. In the human skeletal muscle Rnf28 (equivalent to Murf-1 in rats) is expressed as a muscle-specific E3-ligase. We have previously described increased levels of Murf-1 expression in a rat model of chronic heart failure (CHF) which indicates an accelerated protein catabolism.
Aim of this ongoing prospective randomized trial is to establish the effects of a 4-week supervised ergometer training on Rnf28 expression in skeletal muscle biopsies of patients with stable CHF and healthy subjects (HS).
Methods: A total of 12 CHF-patients and 15 HS were prospectively randomized to a training or to a control group. Before and after the 4-week study period exercise tolerance was quantified by ergospirometry, left ventricular ejection fraction (EF) was assessed by echocardiography, and muscle biopsies were obtained from the vastus lateralis muscle. Rnf28 expression was quantified by real-time PCR and standardized for 18S-rRNA.
Healthy subjects (age 64.0±2.5 years, BMI 27.3±0.8, LV-EF 63±1%): After four weeks of training maximal oxygen uptake (VO2 max) increased from 20.4±1.6 to 24.8±1.8 mL/kg min (p<0.05). In the training group Rnf28 decreased by 31% from 0.48±0.06 to 0.33±0.08 relative units (RU)(p=0.07) while remaining unchanged in the control group.
CHF patients (age 57.4±3.9 years, BMI 29.5±1.5, LV-EF 25±2%): After four weeks of training VO2 max increased from 15.0±1.5 to 16.9±1.9 mL/kg min (p<0.05) and LV-EF increased from 25±3% to 37±2% (p=0.002). At baseline Rnf28 expression was significantly higher as compared to HS (1.00±0.24 vs. 0.41±0.06 RU, p=0.01).
After training Rnf28 decreased by 56% from 1.17±0.31 to 0.51±0.11 RU (p<0.05) while remaining unchanged in the control group.
Conclusions: A four week exercise training program significantly reduces Rnf28 expression and proteasome-mediated protein catabolism in CHF patients. The anticatabolic effect seems to be more pronounced in CHF patients who start from higher Rnf28 expression levels and show greater relative reductions as compared to HS. These results underscore the potential of training interventions to prevent CHF-related cachexia.