Abstract 15352: ELABELA/Toddler, a Critical Regulator of Cardiac Development, is Expressed in the Human Cardiovascular System and Binds the Apelin Receptor
Introduction: ELABELA/Toddler (ELA) (a.k.a. Ende/APELA), a recently identified peptide from a previously designated non-coding region, is expressed in human stem cells and is reported to regulate zebrafish cardiac development. Hearts fail to develop after ELA gene deletion, phenocopying apelin receptor knock-outs. Dibasic cleavage sites predict the expression of 3 isoforms; ELA-32, ELA-21 and ELA-11. Binding of ELA to the human apelin receptor, expression of ELA in the human cardiovascular system, and the functional role of ELA in vivo have not been determined.
Hypothesis: We hypothesised ELA is a ligand for the apelin receptor, endogenously expressed in adult human heart and vessels, and attenuates AngII induced pressor responses.
Methods: Peptides were tested in [125I]apelin-13 competition assays. RT-qPCR and immunocytochemistry with selective antisera were performed in adult human normal cardiovascular tissues (IRB approval). The attenuation of AngII (1μg/kg iv)-induced rise in blood pressure by ELA-32 (176μg/kg iv) or apelin-13 (100μg/kg iv) was compared in anesthetised male C57BL/6 mice.
Results: ELA-32 and ELA-21 competed with IC50 values comparable to apelin-13 (~of 2nM), whereas ELA-11 was 60nM (n=4). ELA mRNA and immunoreactivity were detected in human heart and vessels (n=3-9) with ELA immunoreactivity localised to endothelium. ELA (8.4±0.6mmHg) and apelin (6.1±0.8mmHg) (n=4 each) attenuated the rise in systolic blood pressure caused by AngII, significantly more than the reduction between consecutive AngII doses (2.3±0.4mmHg, 3 repeats) (Fig. 1).
Conclusions: This is the first report of ELA expression in human cardiovascular tissues, high affinity binding to the apelin receptor and action on blood pressure regulation in vivo. These findings demonstrate that novel peptide mediators from previously designated non-coding regions may contribute to human cardiovascular physiology.
Author Disclosures: P. Yang: None. J.J. Maguire: None. R.E. Kuc: None. K. Siew: None. L. Haris Shaikh: None. R. Torella: None. R.C. Glen: None. A.P. Davenport: None.
- © 2014 by American Heart Association, Inc.