Abstract 232: Bendavia, a Novel Mitochondria Targeting Peptide, Improves Mitochondrial Function in Circulating Blood Monocytes From Dogs With Chronic Heart Failure
Background: Mitochondrial (MITO) function is abnormal in heart failure (HF) as evidenced by reduced MITO respiration and rate of ATP synthesis. We showed that MITO dysfunction can be normalized in HF dogs after therapy with Bendavia (BEN), a novel MITO targeting peptide. This study tested the hypothesis that BEN will also reverse abnormalities of MITO function present in blood monocytes (MCs) of HF dogs.
Methods: Blood samples obtained from 6 normal (NL) dogs and 6 dogs with coronary microembolizations-induced HF (LV ejection fraction ~30%) were used to isolate MCs by sequential Ficoll and Percoll density gradients. An XFe/XF96 analyzer (Seahorse Bioscience) was used to measure oxygen consumption rates (OCR) in MCs in the presence and absence of 1 μM oligomycin, 0.5 μM FCCP, or 1 μM each rotenone and antimycin. MITO proton leak, maximal respiration (MAXresp) and spare respiratory capacity (SRC) were measure in the presence and absence of 0.1, 1.0 and 10 μM concentrations of BEN and results expressed in pmols OCR/min/μg protein.
Results: Proton leak, MAXresp and SRC were abnormal in MCs of HF dogs compared to NL. Incubation with BEN had no effect on measures of MCs MITO function of NL dogs but nearly normalized MITO function of MCs of HF dogs as evidenced by a dose-dependent increase MAXresp and SRC and dose-dependent decrease in proton leak (Table).
Conclusions: MITO function is abnormal in blood MCs of HF dogs. BEN had no effect on MITO function of MCS from NL dogs but normalized MITO function in MCs from HF dogs. These findings support the use of circulating blood MCs as means of assessing MITO dysfunction in HF and as a marker of potential benefits derived from treatment with MITO targeted therapies.
Author Disclosures: H.N. Sabbah: 2. Research Grant; Significant; Stealth Peptides, Inc.. 8. Consultant/Advisory Board; Modest; Stealth Peptides, Inc.. V. Sing-Gupta: None. R.C. Gupta: None.
- © 2015 by American Heart Association, Inc.