Heart failure-induced diaphragm myopathy

Area of Science:

• Cardiovascular Physiology
• Skeletal Muscle Biology
• Molecular Cardiology

Background:

• Intracellular signaling pathways governing skeletal myosin heavy chain (MyHC) isoform alterations in heart failure (HF) remain incompletely understood.
• This study investigated changes in diaphragm mitogen-activated protein kinases (MAPK) and myogenic regulatory factors in rats with myocardial infarction (MI)-induced HF.

Purpose of the Study:

• To test the hypothesis that diaphragm MyHC expression and related signaling pathways are altered in rats with MI-induced HF.
• To correlate diaphragm MyHC isoform shifts with cardiac dysfunction and inflammatory markers.

Main Methods:

• Myocardial infarction (MI) was induced in rats, followed by echocardiography to assess cardiac function six months post-MI.
• Infarcted rats were categorized into groups with (MI/HF+) and without (MI/HF-) HF evidence; sham-operated rats served as controls.
• Diaphragm MyHC isoforms were analyzed via electrophoresis; MAPK and myogenic regulatory factors were assessed.

Main Results:

• A significant fast-to-slow shift in diaphragm MyHC isoforms was observed in MI/HF+ rats compared to controls, with MyHC I increasing and MyHC IIb decreasing.
• Left atrial diameter and TNF-α serum levels positively correlated with MyHC I expression.
• Reduced total and phosphorylated ERK levels were noted in both MI/HF- and MI/HF+ groups compared to sham controls.

Conclusions:

• Diaphragm MyHC fast-to-slow transition is linked to cardiac dysfunction severity and elevated TNF-α in infarcted rats.
• Decreased ERK expression appears to contribute to the observed MyHC isoform alterations.
• Myogenic regulatory factors and NF-κB do not seem to mediate diaphragm MyHC distribution changes in chronic HF.