Abstract 15942: Mitochondria-targeted Peptides Attenuate Myocardial Vascular Impairment in Porcine Metabolic Syndrome
Introduction: The metabolic syndrome (MetS) leads to cardiac injury, partly due to increased myocardial oxidative stress. The novel mitochondria-targeted peptide MTP-131 shows cardio-protective properties in experimental ischemic disease.
Hypothesis: We hypothesized that MTP-131 would restore mitochondrial antioxidant activity and decrease cardiac vascular injury in porcine MetS.
Methods: Pigs were studied after 16wks of diet-induced MetS, MetS treated for the last 4wks with MTP-131 (Elamipretide, 0.1mg/kg SC q.d), and lean controls (n=6 each). Myocardial oxygenation (Blood Oxygen Level Dependent-MRI) was then assessed in-vivo, and oxidative stress (oxidized-LDL, isoprostanes), coronary endothelial function (organ bath), myocardial mitochondrial antioxidant activity (NADPH/NADH ratio), and microvascular density (micro-CT) ex-vivo.
Results: MetS pigs had elevated cholesterol, blood pressure, and insulin resistance (Table). Circulating isoprostane and myocardial oxidized-LDL expression were elevated in MetS, but decreased in MetS+MTP-131, and mitochondrial NADPH/NADH was restored (Figure), suggesting decreased mitochondrial oxidative stress. MTP-131 also attenuated myocardial microvascular loss, hypoxia, and coronary endothelial dysfunction.
Conclusion: Chronic treatment with MTP-131 attenuated microvascular loss, endothelial dysfunction, and myocardial hypoxia. These effects might be mediated partly by ameliorating mitochondrial oxidative stress, underscoring the role of mitochondria in regulating the cardiac circulation in experimental MetS.
Author Disclosures: F. Yuan: None. A.F. Hedayat: None. C.M. Ferguson: None. A. Lerman: Consultant/Advisory Board; Modest; Stealth Peptides International, Incorporated. L.O. Lerman: Research Grant; Modest; Stealth Peptides International, Incorporated. A. Eirin: None.
- © 2016 by American Heart Association, Inc.