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Publication:
Heart Failure-Induced Diaphragm Myopathy

Abstract

Background: Intracellular signaling pathways involved in skeletal myosin heavy chain (MyHC) isofornn 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 isofornns 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-kappa B 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 isofornn changes. Myogenic regulatory factors and NF-kappa B do not modulate diaphragm MyHC distribution during chronic HF. Copyright (C) 2014 S. Karger AG, Basel

Description

Keywords

Skeletal muscle, MAPK, Myogenic regulatory factors, Myosin heavy chain isoforms, Echocardiography, Myocardial infarction

Language

English

Citation

Cellular Physiology And Biochemistry. Basel: Karger, v. 34, n. 2, p. 333-345, 2014.

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