Title

Chronic Therapy With Elamipretide (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves Left Ventricular and Mitochondrial Function in Dogs With Advanced Heart Failure.

Document Type

Article

Publication Date

2-1-2016

Publication Title

Circ Heart Fail

Abstract

BACKGROUND: Elamipretide (MTP-131), a novel mitochondria-targeting peptide, was shown to reduce infarct size in animals with myocardial infarction and improve renal function in pigs with acute and chronic kidney injury. This study examined the effects of chronic therapy with elamipretide on left ventricular (LV) and mitochondrial function in dogs with heart failure (HF).

METHODS AND RESULTS: Fourteen dogs with microembolization-induced HF were randomized to 3 months monotherapy with subcutaneous injections of elamipretide (0.5 mg/kg once daily, HF+ELA, n=7) or saline (control, HF-CON, n=7). LV ejection fraction, plasma n-terminal pro-brain natriuretic peptide, tumor necrosis factor-α, and C-reactive protein were measured before (pretreatment) and 3 months after initiating therapy (post-treatment). Mitochondrial respiration, membrane potential (Δψm), maximum rate of ATP synthesis, and ATP/ADP ratio were measured in isolated LV cardiomyocytes obtained at post-treatment. In HF-CON dogs, ejection fraction decreased at post-treatment compared with pretreatment (29 ± 1% versus 31 ± 2%), whereas in HF+ELA dogs, ejection fraction significantly increased at post-treatment compared with pretreatment (36 ± 2% versus 30 ± 2%; P

CONCLUSIONS: Long-term therapy with elamipretide improves LV systolic function, normalizes plasma biomarkers, and reverses mitochondrial abnormalities in LV myocardium of dogs with advanced HF. The results support the development of elamipretide for the treatment of HF.

Medical Subject Headings

Animals; Biomarkers; C-Reactive Protein; Disease Models, Animal; Dogs; Energy Metabolism; Heart Failure; Infusions, Intravenous; Injections, Subcutaneous; Membrane Potential, Mitochondrial; Mitochondria, Heart; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oligopeptides; Peptide Fragments; Reactive Oxygen Species; Recovery of Function; Stroke Volume; Time Factors; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left; Ventricular Function, Left

PubMed ID

26839394

Volume

9

Issue

2

First Page

002206

Last Page

002206

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