title: Heart failure-induced diaphragm myopathy.
abstract: BACKGROUND
  Intracellular signaling pathways involved in skeletal myosin heavy chain (MyHC) isoform alterations during heart failure (HF) are not completely understood. We tested the hypothesis that diaphragm expression of mitogen-activated protein kinases (MAPK) and myogenic regulatory factors is changed in rats with myocardial infarction (MI) induced HF.
  
  
  METHODS
  Six months after MI rats were subjected to transthoracic echocardiography. After euthanasia, infarcted rats were subdivided in MI/HF- group (with no HF evidence; n=10), and MI/HF+ (with right ventricular hypertrophy and lung congestion; n=10). Sham-operated rats were used as controls (n=10). MyHC isoforms were analyzed by electrophoresis.
  
  
  METHODS
  ANOVA and Pearson correlation.
  
  
  RESULTS
  MI/HF- had left cardiac chambers dilation with systolic and diastolic left ventricular dysfunction. Cardiac injury was more intense in MI/HF+ than MI/HF-. MyHC I isoform percentage was higher in MI/HF+ than MI/HF-, and IIb isoform lower in MI/HF+ than Sham. Left atrial diameter-to-body weight ratio positively correlated with MyHC I (p=0.005) and negatively correlated with MyHC IIb (p=0.02). TNF-α serum concentration positively correlated with MyHC I isoform. Total and phosphorylated ERK was lower in MI/HF- and MI/HF+ than Sham. Phosphorylated JNK was lower in MI/HF- than Sham. JNK and p38 did not differ between groups. Expression of NF-κB and the myogenic regulatory factors MyoD, myogenin, and MRF4 was similar between groups.
  
  
  CONCLUSIONS
  Diaphragm MyHC fast-to-slow shift is related to cardiac dysfunction severity and TNF-α serum levels in infarcted rats. Reduced ERK expression seems to participate in MyHC isoform changes. Myogenic regulatory factors and NF-κB do not modulate diaphragm MyHC distribution during chronic HF.
authors: Internal Medicine Department, Botucatu Medical School - UNESP, Botucatu, SP, Brazil.
authors: Aline Regina Ruiz
authors: AR
authors: Lima
authors: Paula Felippe
authors: PF
authors: Martinez
authors: Ricardo Luiz
authors: RL
authors: Damatto
authors: Marcelo Diarcadia Mariano
authors: MD
authors: Cezar
authors: Daniele Mendes
authors: DM
authors: Guizoni
authors: Camila
authors: C
authors: Bonomo
authors: Silvio Assis
authors: SA
authors: Oliveira
authors: Maeli
authors: M
authors: Dal-Pai Silva
authors: Leonardo Antonio Mamede
authors: LA
authors: Zornoff
authors: Katashi
authors: K
authors: Okoshi
authors: Marina Politi
authors: MP
authors: Okoshi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003964:Diaphragm / Q000473:pathology*; D004452:Echocardiography; D006333:Heart Failure / Q000150:complications* / Q000000981:diagnostic imaging; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009135:Muscular Diseases / Q000209:etiology*; D009203:Myocardial Infarction / Q000150:complications* / Q000000981:diagnostic imaging; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha