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54 A significant proportion of heart failure patients develop skeletal muscle wasting and cardiac 55 cachexia, which is associated with a very poor prognosis. Recently, myostatin–a cytokine 56 from the TGF-β family and a known strong inhibitor of skeletal muscle growth–has been 57 identified as a direct mediator of skeletal muscle atrophy in mice with heart failure. 58 Myostatin is mainly expressed in skeletal muscle, although basal expression is also detectable 59 in heart and adipose tissue. During pathological loading of the heart, the myocardium 60 produces and secretes myostatin into the circulation where it inhibits skeletal muscle growth. 61 Thus, genetic elimination of myostatin from the heart reduces skeletal muscle atrophy in mice 62 with heart failure, while transgenic overexpression of myostatin in the heart is capable of 63 inducing muscle wasting. In addition to its endocrine action on skeletal muscle …