Myostatin produced by the failing heart mediates skeletal muscle atrophy, and its direct inhibition positively impacts skeletal muscle mass, suggesting a promising treatment for cardiac cachexia.
Does myostatin inhibition prevent skeletal muscle wasting in heart failure?
Myostatin acts as an endocrine factor secreted by the failing heart to induce skeletal muscle wasting, highlighting its inhibition as a promising therapeutic target for cardiac cachexia.
A significant proportion of heart failure patients develop skeletal muscle wasting and cardiac cachexia, which is associated with a very poor prognosis. Recently, myostatin, a cytokine from the transforming growth factor-β (TGF-β) family and a known strong inhibitor of skeletal muscle growth, has been identified as a direct mediator of skeletal muscle atrophy in mice with heart failure. Myostatin is mainly expressed in skeletal muscle, although basal expression is also detectable in heart and adipose tissue. During pathological loading of the heart, the myocardium produces and secretes myostatin into the circulation where it inhibits skeletal muscle growth. Thus, genetic elimination of myostatin from the heart reduces skeletal muscle atrophy in mice with heart failure, whereas transgenic overexpression of myostatin in the heart is capable of inducing muscle wasting. In addition to its endocrine action on skeletal muscle, cardiac myostatin production also modestly inhibits cardiomyocyte growth under certain circumstances, as well as induces cardiac fibrosis and alterations in ventricular function. Interestingly, heart failure patients show elevated myostatin levels in their serum. To therapeutically influence skeletal muscle wasting, direct inhibition of myostatin was shown to positively impact skeletal muscle mass in heart failure, suggesting a promising strategy for the treatment of cardiac cachexia in the future.
Breitbart et al. (Sat,) conducted a review in Heart failure and muscle wasting (cardiac cachexia). Myostatin inhibition was evaluated. Myostatin produced by the failing heart mediates skeletal muscle atrophy, and its direct inhibition positively impacts skeletal muscle mass, suggesting a promising treatment for cardiac cachexia.