title: Anabolic effects of exercise training in patients with advanced chronic heart failure (NYHA IIIb): impact on ubiquitin-protein ligases expression and skeletal muscle size.
abstract: Patients with advanced chronic heart failure (CHF) are characterized by progressive muscle wasting. The two E3-ligases Rnf28 and Atrogin-1 controlling the activation of the ubiquitinproteasome system might be of importance for the regulation of muscle size. Given the convincing effect of regular physical exercise training (ET) in CHF, it was the aim of the present trial to elucidate, whether ET affects both mentioned enzymes in CHF and whether this is associated with an increase in skeletal muscle mass.
  
  
  METHODS
  37 patients with severe CHF were randomized to 12 weeks of ET or sedentary lifestyle (control). The expression of Rnf28 and Atrogin-1 in the skeletal muscle was analyzed by RT-PCR and Western blotting. Skeletal muscle cross sectional area (CSA) was measured by computed tomography.
  
  
  RESULTS
  In CHF patients ET led to a significant reduction in skeletal muscle mRNA transcription (from 14.3 ± 2.0 to 8.7 ± 1.4 arbitrary units; p<0.05 versus baseline and versus control for the change) and protein expression of Rnf28 (from 4.70 ± 1.35 to 2.84 ± 0.65 arbitrary units; p<0.05 versus baseline and versus control for the change). This was accompanied by a significant increase in total muscle CSA of both thighs (from 139.9 ± 5.2 to 149.2 ± 5.9 cm(2); p<0.05 versus baseline and versus control for the change). On the contrary, Atrogin-1 was not affected.
  
  
  CONCLUSIONS
  In patients with advanced CHF, regular physical exercise training led to a decrease in Rnf28 expression in the skeletal muscle. This was linked to an increase in skeletal muscle cross sectional area, supporting the notion that ET has anti-catabolic properties in CHF.
authors.affiliation: Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany. Robert.Hoellriegel@med.uni-leipzig.de
authors.forename: Robert
authors.initials: R
authors.lastname: Höllriegel
authors.forename: Ephraim B
authors.initials: EB
authors.lastname: Beck
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.forename: Sven
authors.initials: S
authors.lastname: Möbius-Winkler
authors.forename: Norman
authors.initials: N
authors.lastname: Mangner
authors.forename: Marcus
authors.initials: M
authors.lastname: Sandri
authors.forename: Stephan
authors.initials: S
authors.lastname: Gielen
authors.forename: Matthias
authors.initials: M
authors.lastname: Gutberlet
authors.forename: Rainer
authors.initials: R
authors.lastname: Hambrecht
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
authors.forename: Sandra
authors.initials: S
authors.lastname: Erbs
mesh_terms: D002908:Chronic Disease; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test / Q000379:methods*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000201:enzymology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000201:enzymology*; D009929:Organ Size / Q000502:physiology; D011859:Radiography; D057185:Sedentary Behavior; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis*
chemical_list: D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases