title: Reduction of insulin-like growth factor-I expression in the skeletal muscle of noncachectic patients with chronic heart failure.
abstract: OBJECTIVE
  We sought to assess the role of insulin-like growth factor-I (IGF-I) in muscle wasting in chronic heart failure (CHF), serum concentrations and local muscular IGF-I expression were determined in patients with severe CHF.
  
  
  BACKGROUND
  Chronic heart failure is associated with progressive muscle atrophy, leading to cardiac cachexia. Skeletal muscle disuse and inflammatory activation with elevated cytokine levels have been implicated; however, the pathomechanism involved remains largely unknown.
  
  
  METHODS
  Serum levels of IGF-I were measured by competitive solid phase immunoassay in 47 patients with severe CHF (left ventricular ejection fraction < or =30%) and 15 age-matched healthy subjects (HS). Insulin-like growth factor-I and IGF-I receptor expression were assessed in vastus lateralis biopsies by real-time PCR and Western blot analysis.
  
  
  RESULTS
  Although serum IGF-I was not significantly different (175 +/- 10 ng/ml in CHF vs. 170 +/- 12 ng/ml in HS, p = NS), local muscle IGF-I mRNA expression was reduced by 52% in CHF (6.7 +/- 0.4 vs. 14.0 +/- 0.9 arbitrary units in HS, p < 0.001). This was accompanied by an increase in IGF-I receptor mRNA expression (86.8 +/- 5.4 in CHF vs. 23.1 +/- 1.8 arbitrary units in HS, p < 0.001). Local IGF-I expression was significantly correlated with muscle cross-sectional area (R = 0.75, p = 0.01). Chronic heart failure patients with a body mass index of < 25 kg/m(2) showed signs of peripheral growth hormone (GH) resistance, as indicated by elevated serum GH, and reduced IGF-I levels.
  
  
  CONCLUSIONS
  In CHF patients, muscle IGF-I expression is considerably reduced in the presence of normal serum IGF-I levels, possibly contributing to early loss of muscle mass. These findings are consistent with a potential role of IGF-I for skeletal muscle atrophy in CHF.
authors.affiliation: University of Leipzig-Heart Center, Department of Cardiology, Leipzig, Germany. hamr@medizin.uni-leipzig.de
authors.forename: Rainer
authors.initials: R
authors.lastname: Hambrecht
authors.forename: Paul Christian
authors.initials: PC
authors.lastname: Schulze
authors.forename: Stephan
authors.initials: S
authors.lastname: Gielen
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.forename: Sven
authors.initials: S
authors.lastname: Möbius-Winkler
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Yu
authors.forename: J ürgen
authors.initials: Jü
authors.lastname: Kratzsch J
authors.forename: Gerhard
authors.initials: G
authors.lastname: Baldauf
authors.forename: Martin W
authors.initials: MW
authors.lastname: Busse
authors.forename: Andreas
authors.initials: A
authors.lastname: Schubert
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
mesh_terms: D015992:Body Mass Index; D002100:Cachexia / Q000209:etiology; D016022:Case-Control Studies; D006333:Heart Failure / Q000378:metabolism*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I