Abstract 17160: Mots-c: a Novel Mitochondrial-derived Peptide is Associated With Coronary Endothelial Function
Introduction: Coronary endothelial dysfunction is the early stage of atherosclerosis and is associated with cardiovascular events. We previously demonstrated that the mitochondrial peptide (MDP) humanin is associated to preserved coronary endothelial function (CEF) in humans. MOTS-c is a newly discovered MDP that promotes metabolic homeostasis, but its effects on the cardiovascular system have not yet been studied. Here we test the hypothesis that MOTS-c may be related to endothelial function in humans.
Methods: Using a novel in house ELISA for MOTS-c circulating MOTS-c plasma levels were measured in patients with normal (n=20) or abnormal (n=20) CEF, defined as an abnormal response to intracoronary acetylcholine (Ach) challenge. Microvascular coronary endothelial dysfunction was defined as an increase in coronary blood flow (CBF) of <50%, and epicardial endothelial dysfunction as a decrease in epicardial coronary artery diameter (CAD) of <20% in response to maximal Ach dose. Endothelial independent microvascular function was also evaluated by measurement of coronary flow reserve (CFR) in response to intracoronary adenosine. Other parameters such as age, family history, sex and comorbidities were also taken into consideration.
Results: There was no difference in baseline demographics between the two groups. MOTS-c plasma levels were lower in patients with abnormal CEF compared to normal CEF (p=0.007; fig.1A), and were directly correlated with CFR (R2=0.11, p=0.04; fig. 1B), epicardial (R2=0.13, p=0.02; fig. 1C) and microvascular CEF (R2=0.14, p=0.01, fig. 1D). MOTS-c levels tended to decrease with age and to be inversely correlated with BNP.
Conclusions: Circulating MOTS-c plasma levels are correlated with both macro- and microvascular coronary endothelial function. Our study discovers a novel association that supports a role for MOTS-c in cardiovascular diseases in humans.
Author Disclosures: S. Delrio: None. J. Wan: None. P. Cohen: Consultant/Advisory Board; Modest; CohBar Inc. L.O. Lerman: Research Grant; Modest; Stealth Biotherapeutics, Incorporated. Research Grant; Significant; Recombinetics, Inc. A. Lerman: Consultant/Advisory Board; Modest; CohBar.
- © 2016 by American Heart Association, Inc.