Title

ELAMIPRETIDE REDUCES THE BURDEN FOR INDUCTION OF APOPTOSIS IN SKELETAL MUSCLE OF DOGS WITH CHRONIC HEART FAILURE

Document Type

Conference Proceeding

Publication Date

2019

Publication Title

J Am Coll Cardiol

Abstract

Background: Exercise intolerance (Ex-Int) is a feature of heart failure (HF) and is attributed to skeletal muscle (SM) abnormalities including fiber type composition, atrophy, fiber loss, and mitochondrial (MITO) dysfunction. MITO dysfunction can activate apoptosis by releasing cytochrome C (CYTO-C) into the cytosol. We showed that therapy with elamipretide (ELAM) improves MITO function in failing cardiomyocytes and limits the release of CYTO-C into the cytosol. This study examined the effects of ELAM on markers of apoptosis in SM MITO of normal (NL) dogs and dogs with microembolization-induced HF. Methods: Fresh SM biopsy specimen from the Vastus Lateralis muscle of 6 NL and 6 HF dogs were incubated in vehicle solution and in 0.10 μM ELAM for one hour at 37°C. At end of incubation, MITO were isolated from SM and used in Western blots to assess levels of CYTO-C and HtrA2, a proapoptotic MITO serine protease. Protein levels of CYTO-C and HtrA2 were normalized to porin, a MITO protein that is unchanged in HF. Results: Levels of porin were similar in MITO from NL, HF, and ELAM-treated HF dogs (Table). Levels of CYTO-C and HtrA2 were significantly reduced in HF MITO compared to NL. Treatment with ELAM increased protein levels of both CYTO-C and HtrA2 in HF MITO (Table). Conclusion: ELAM partially prevents the translocation of CYTO-C and HtrA2 from MITO to cytosol in SM of HF dogs. ELAM can lower the burden of apoptosis in SM and possibly prevent ongoing loss of muscle mass thus favoring reversal of Ex-Int in HF. [Table presented]

Volume

73

Issue

9 Suppl 1

First Page

821

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