Myostatin and follistatin expression in skeletal muscles of rats with chronic heart failure

Heart failure is characterized by a decreased exercise capacity due to the early appearance of symptoms like dyspnoea and muscle fatigability. Although these symptoms can be caused by reduced cardiac output, there is no clear association between exercise intolerance and hemodynamic parameters (Mancini et al. 1992; Harrington et al. 2001). It has been suggested that intrinsic skeletal muscle abnormalities play a role in decreased exercise capacity and heart failure symptoms (Vescovo et al. 1998). Muscle wasting is common in chronic illnesses such as those associated with HIV infection, some types of cancer, and heart failure (Mancini et al. 1992; Gonzalez-Cadavid et al. 1998; Bruera & Sweeney 2000). The mechanisms responsible for muscle atrophy in heart failure are not clear. Myostatin, a recently identified member of the transforming growth factor beta (TGF-β) superfamily of secreted growth and differentiation factors, regulates muscle growth, acting as a negative regulator of skeletal muscle mass (McPherron et al. 1997; Lee 2004). Several studies have shown a negative correlation between myostatin expression and muscle mass. Mutations of myostatin gene in cattle are associated with muscle hypertrophy (McPherron & Lee 1997). Similarly, myostatin-null mice present increased muscle mass, resulting from both muscle fibre hyperplasia and hyperthrophy (McPherron et al. 1997). Pharmacological treatment with a myostatin antibody increased skeletal muscle mass and grip strength (Whittemore et al. 2003). Furthermore, systemic overexpression of myostatin in adult mice was found to induce profound muscle and fat loss (Zimmers et al. 2002). In a clinical setting, recent investigations have suggested that myostatin may be involved in the muscle mass reduction observed in AIDS and cancer patients (Gonzalez-Cadavid et al. 1998; Acharyya & Gutttridge 2007). In HIV-infected men, increased levels of myostatin immunoreactive material in serum and skeletal muscle appear to correlate with the presence of cachexia (Gonzalez-Cadavid et al. 1998). In heart failure, the role of myostatin on skeletal muscle wasting remains unclear. Recently, Lenk et al. (2009) reported that myostatin was up-regulated in cardiac and skeletal muscle during experimental heart failure. The aim of this study was to evaluate myostatin mRNA and protein expression and skeletal muscle trophism in rats with myocardial infarction-induced heart failure. As myostatin expression can be modulated by follistatin, an antagonistic protein, we also evaluated follistatin expression.