Abstract 20029: Inhibition of Myostatin for the Prevention and Treatment of Cardiac Dysfunction after Aortic Constriction

Introduction: Myostatin (MSTN) is a secreted regulator of skeletal muscle growth recently recognized to increase in cardiac pathologies. MSTN inhibits the pro-survival kinase, Akt, and MSTN-null mice are protected against aging-related cardiac dysfunction and fibrosis. We hypothesized that increased cardiac MSTN is maladaptive and tested whether RAP-031, a murine analog of MSTN inhibitor (ACE-031) currently in clinical trials for skeletal muscle disease, could mitigate cardiac dysfunction after transverse aortic constriction (TAC). Methods: To see if RAP-031 could prevent cardiac dysfunction, wild-type (WT) FVB mice were randomized to RAP-031 (10mg/kg SQ, 2x/week) or vehicle. After 1 week, groups were further randomized to TAC (27G needle) or sham operation (N=5–7). Body weight, body composition by MRI, and cardiac function were followed for 12 weeks. To evaluate if RAP-031 could treat cardiac dysfunction, WT mice underwent TAC and when fractional shortening (FS) was ≥2STD below baseline were randomized t...