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Myostatin signaling is up-regulated in female patients with advanced heart failure
Junichi Ishida1, Masaaki Konishi1, Masakazu Saitoh1
1Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany.
Insights
Heart failure (HF) involves increased myostatin in females, linked to weight loss. This study found myostatin and pSmad2 up-regulation in female HF hearts, suggesting a role in cardiac cachexia pathogenesis.
Area of Science:
- Cardiology
- Molecular Biology
- Endocrinology
Background:
- Myostatin negatively regulates skeletal muscle mass.
- Myostatin is elevated in heart failure (HF) myocardium and linked to weight loss in animal models.
- Gender-specific differences in HF pathophysiology and myostatin expression remain unclear.
Purpose of the Study:
- To investigate gender differences in myostatin expression in human heart failure.
- To determine if myostatin expression is associated with weight loss in HF patients.
- To explore the role of myostatin signaling in the pathogenesis of HF and cardiac cachexia.
Main Methods:
- Heart tissue samples were obtained from HF patients (n=31) and healthy controls (n=14).
- Western blotting was used to analyze the expression of myostatin and related proteins.
- Body mass index (BMI) was compared between male and female HF patients.
Main Results:
- Female HF patients had a significantly lower BMI than male HF patients (20.0±4.2 vs 25.2±3.8, p=0.04).
- Mature myostatin and pSmad2 were significantly upregulated in female HF hearts compared to female donors (1.9-fold, p=0.05 and 2.5-fold, p<0.01, respectively).
- pSmad2 was upregulated in male HF patients, but myostatin was not; no significant gender differences in myostatin signaling protein expression were observed between HF patients.
Conclusions:
- Myostatin and pSmad2 are significantly upregulated in the failing hearts of female HF patients, but not male patients.
- Female HF patients exhibit lower body mass index.
- Enhanced myostatin signaling in the female failing heart may contribute to HF pathogenesis and cardiac cachexia.
Background:
Myostatin, a negative regulator of skeletal muscle mass, is up-regulated in the myocardium of heart failure (HF) and increased myostatin is associated with weight loss in animal models with HF. Although there are disparities in pathophysiology and epidemiology between male and female patients with HF, it remains unclear whether there is gender difference in myostatin expression and whether it is associated with weight loss in HF patients.
Methods:
Heart tissue samples were collected from patients with advanced heart failure (n=31, female n=5) as well as healthy control donors (n=14, female n=6). Expression levels of myostatin and its related proteins in the heart were evaluated by western blotting analysis.
Results:
Body mass index was significantly lower in female HF patients than in male counterparts (20.0±4.2 in female vs 25.2±3.8 in male, p=0.04). In female HF patients, both mature myostatin and pSmad2 were significantly up-regulated by 1.9 fold (p=0.05) and 2.5 fold (p<0.01) respectively compared to female donors, while expression of pSmad2 was increased by 2.8 times in male HF patients compared to male healthy subjects, but that of myostatin was not. There was no significant difference in protein expression related to myostatin signaling between male and female patients.
Conclusion:
In this study, myostatin and pSmad2 were significantly up-regulated in the failing heart of female patients, but not male patients, and female patients displayed lower body mass index. Enhanced myostatin signaling in female failing heart may causally contribute to pathogenesis of HF and cardiac cachexia.
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