Key result
Myocardial infarction-induced heart failure in rats was associated with a diaphragm MyHC fast-to-slow shift related to cardiac dysfunction severity and TNF-α levels, and reduced ERK expression.
In a rat model of MI-induced HF, diaphragm MyHC fast-to-slow shift is related to cardiac dysfunction severity and TNF-α levels, with reduced ERK expression likely participating in these changes.
May link cardiac dysfunction to respiratory impairment in HF; leaves open TNF-α/ERK targeting pending human validation.
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.
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Lima et al. (2014) studied Myocardial infarction induced heart failure (n=30). Myocardial infarction induced heart failure vs. Sham-operated rats was evaluated on Diaphragm expression of MAPK, myogenic regulatory factors, and MyHC isoforms. Myocardial infarction-induced heart failure in rats was associated with a diaphragm MyHC fast-to-slow shift related to cardiac dysfunction severity and TNF-α levels, and reduced ERK expression.
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