Abstract 12980: Circulating Level of the Growth-Differentiation Factor-15 Is Increased in Dogs With Heart Failure and Normalized After Long-term Therapy With Elamipretide
Introduction: Growth-differentiation factor-15 (GDF15) is a stress-responsive cytokine produced in pathological states associated with tissue injury and inflammation. Increased level of GDF15 is an independent predictor of adverse prognosis (disease progression and mortality) in heart failure (HF). As a prognostic biomarker, GDF15 is independent of established biomarkers including BNP, troponins, or C-reactive protein (CRP). We previously showed that increased plasma levels of nt-pro BNP, tumor necrosis factor-α, interleukin-6 and CRP are normalized in dogs with HF following long-term therapy with Elamipretide (ELA, BendaviaTM), a novel mitochondria targeting peptide. We also showed that therapy with ELA also prevents progressive LV dysfunction in dogs with HF.
Hypothesis: This study tested the hypothesis that plasma level of GDF15 is increased in dogs with HF and is normalized after long-term therapy with ELA.
Methods: Venous blood samples were obtained from 14 dogs at baseline (normal state) prior to induction of HF, after the induction of HF by intracoronary microembolizations but prior to any therapy and again at 3 months after initiating therapy with either subcutaneous ELA (0.5 mg/kg/day, n=7) or saline v/v (Control, n=7). Plasma levels of GDF15 were measured using a dog specific commercially available enzyme-linked immunosorbent assay (ELISA) kit (MyBiosource, San Diego, CA).
Results: In untreated HF control dogs, plasma level of GDF15 was 326±32 pg/ml at baseline and increased to 744±124 pg/ml (p<0.05) when dogs were in HF and remained elevated at 3 months after initiating therapy with saline (728± 77 pg/ml). In dogs treated with ELA, plasma level of GDF15 was 314±29 pg/ml at baseline, increased to 875±71 pg/ml (p<0.05) when dogs were in HF and was restored to near normal levels at 3 months after initiating therapy with ELA (556±25 pg/ml, p<0.05 vs. pre-treatment).
Conclusions: Circulating levels of GDF15 are increased in dogs with coronary microembolizations-induced HF. Long-term treatment with ELA reverses this increase, suggesting that inflammation-mediated injury may be reduced in dogs with HF treated with ELA. Restoring GDF15 by ELA therapy may be a useful indicator of beneficial response to therapy in patients with chronic HF.
Author Disclosures: H.N. Sabbah: None. R.C. Gupta: None. V. Singh-Gupta: None. K. Zhang: None. J. Xu: None.
- © 2016 by American Heart Association, Inc.