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Heart failure-induced diaphragm myopathy.

Authors: Lima, AR  Martinez, PF  Damatto, RL  Cezar, MD  Guizoni, DM  Bonomo, C  Oliveira SA, JR  Dal-Pai Silva, M  Zornoff, LA  Okoshi, K  Okoshi, MP 
Citation: Lima AR, etal., Cell Physiol Biochem. 2014;34(2):333-45. doi: 10.1159/000363003. Epub 2014 Jul 8.
Pubmed: (View Article at PubMed) PMID:25060722
DOI: Full-text: DOI:10.1159/000363003

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. STATISTICAL ANALYSIS: 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-alpha 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-kappaB and the myogenic regulatory factors MyoD, myogenin, and MRF4 was similar between groups. CONCLUSION: Diaphragm MyHC fast-to-slow shift is related to cardiac dysfunction severity and TNF-alpha serum levels in infarcted rats. Reduced ERK expression seems to participate in MyHC isoform changes. Myogenic regulatory factors and NF-kappaB do not modulate diaphragm MyHC distribution during chronic HF.

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CRRD Object Information
CRRD ID: 9686065
Created: 2015-01-29
Species: All species
Last Modified: 2015-01-29
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.