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.

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-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.

CONCLUSION:

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: Aline Regina Ruiz Lima, Paula Felippe Martinez, Ricardo Luiz Damatto, Marcelo Diarcadia Mariano Cezar, Daniele Mendes Guizoni, Camila Bonomo, Silvio Assis Oliveira Jr, Maeli Dal-Pai Silva, Leonardo Antonio Mamede Zornoff, Katashi Okoshi, Marina Politi Okoshi
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 34 Issue 2 Pg. 333-45 ( 2014) ISSN: 1421-9778 [Electronic] Germany
• PMID: 25060722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Interleukin-6
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Blotting, Western
• Diaphragm (pathology)
• Echocardiography
• Heart Failure (complications, diagnostic imaging)
• Interleukin-6 (blood)
• Male
• Muscular Diseases (etiology)
• Myocardial Infarction (complications, diagnostic imaging)
• Rats
• Rats, Wistar
• Real-Time Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (blood)