Abstract 15744: Normalization of Plasma Pro-Inflammatory Cytokines Following Long-Term Therapy With Bendavia (MTP-131) in Dogs With Advanced Heart Failure
Background: Heart failure (HF) is often described as a complex neurohumoral and inflammatory syndrome. Cytokines including interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) can adversely impact cardiac function by promoting LV remodeling, inducing contractile dysfunction through suppression of mitochondrial respiration and by uncoupling β-adrenergic receptors. We previously showed that chronic therapy with Bendavia (MTP-13), a novel mitochondria targeting peptide, improves LV function and normalizes the rate of ATP synthesis by mitochondria. This study examined the effects of chronic therapy with Bendavia on plasma levels of IL-6, TNF-α, and the pro-inflammatory marker c-reactive protein (CRP) 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 levels of IL-6, TNF-α, and CRP were measured 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. IL-6, TNF-α and CRP levels were determined using commercially available enzyme-linked immunoassay (ELISA) kits and standard curves.
Results: Data are shown in Table. Levels of IL-6, TNF-α, and CRP increased significantly in all dogs after establishment of HF compared to BL. Treatment with Bendavia in significantly reduced levels of all 3 inflammatory proteins at W-6 and nearly normalized the levels at W-12. In untreated controls, plasma levels of IL-6, TNF-α, and CRP remained markedly elevated throughout the treatment phase.
Conclusions: In dogs with HF, long-term therapy with Bendavia is associated with suppression of the pro-inflammatory state. This beneficial effect of Bendavia is likely the indirect consequence of its ability to improve mitochondrial function and overall LV performance.
- © 2013 by American Heart Association, Inc.