Abstract 12882: Monotherapy With Bendavia (MTP-131), a Novel Mitochondria-Targeting Peptide, Normalizes H11 Kinase Protein Levels in Nuclear and Mitochondrial Fractions of Left Ventricular Myocardium of Dogs With Advanced Heart Failure

Introduction: The heat shock protein H11 kinase (H11K) is expressed in the heart and rapidly increases in response to increased cardiac workload. Deletion of H11K accelerates LV dysfunction and remodeling by deactivating STAT3, a stress-inducible transcription factor. Deactivation of STAT3 has been shown to adversely impact mitochondrial function. We previously showed that chronic therapy (3 months) with Bendavia (BEN, MTP-131), a novel mitochondria-targeting peptide, improves LV function in dogs with heart failure (HF) and normalizes mitochondrial respiration and rate of ATP synthesis. Hypothesis: This study tested the hypothesis that H11K protein level is reduced in mitochondrial (MF) and nuclear fractions (NF) of the failing LV and normalized after therapy with BEN. Methods: LV tissue was obtained from 12 dogs with microembolization-induced HF (LV ejection fraction ~30%) randomized to 3 months therapy with subcutaneous injections of BEN (0.5 mg/kg once daily, n=6) or saline (HF-Control, n=6). LV tissue...