Abstract 12891: Long-term Therapy with Bendavia (MTP-131), a Novel Mitochondria-Targeting Peptide, Reduces Total Burden of Reactive Oxygen Species in Plasma of Dogs with Advanced Heart Failure
Background: Reactive oxygen species (ROS) burden is increased in heart failure (HF) and can overwhelm endogenous antioxidant defenses leading to damage of cellular lipids, proteins, and DNA and ultimately cell death. Lipid peroxidation, for example, is a well-characterized effect of ROS that results in damage to the inner and outer mitochondria (MITO) membranes. Previous studies in animal models of infarction and HF showed that chronic therapy with Bendavia (MTP-131), a novel MITO targeting peptide, improves LV function, normalizes MITO function, MITO rate of ATP synthesis and electron flux through the electron transport chain (ETC). This study examined the effects of long-term therapy with Bendavia on plasma ROS burden in dogs with coronary microembolization-induced HF (LV ejection fraction ~30%).
Methods: HF dogs (n=14) were randomized to 3 months monotherapy with subcutaneous injections of Bendavia (0.5 mg/kg once daily, n=7) or no therapy at all (control, n=7). Plasma ROS was assessed at baseline (BL), prior to induction of HF, after induction of HF at time of randomization (pre-treatment, PRE) and after 6 weeks (W-6) and 12 weeks (W-12) of therapy. ROS levels were evaluated luminometrically using a commercially available kit and expressed in relative luminescence units (RLUx105) /ml.
Results: Data are shown in the Table. ROS plasma levels increased nearly 4-fold in both study groups at PRE compared to BL. b Bendavia significantly decreased ROS levels at W-6 and more profoundly at W-12. Plasma ROS levels remained elevated in untreated control dogs.
Conclusions: Long-term therapy with Bendavia normalizes ROS levels in plasma of dogs with advanced HF. This is likely the indirect consequence of Bendavia’s ability to improve electron flux through the ETC and reduce electron leak from the respiratory chain. Alleviating ROS burden likely contributed, albeit in part, to improved MITO function and consequently to improved LV function following treatment with Bendavia.
- © 2013 by American Heart Association, Inc.