Myostatin signaling is up-regulated in female patients with advanced heart failure

Background: Myostatin, a negative regulator of skeletal muscle mass, is up-regulated in the myocardiumof heart failure (HF) and increasedmyostatin is associatedwithweight 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 sampleswere collected frompatientswith 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 inmale 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 pSmad2was increased by 2.8 times inmale HF patients compared to male healthy subjects, but that of myostatinwas not. Therewas no significant difference in protein expression related tomyostatin 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 notmale patients, and female patients displayed lower body mass index. Enhancedmyostatin signaling in female failing heart may causally contribute to pathogenesis of HF and cardiac cachexia. (C) 2017 Elsevier B. V. All rights reserved.