Apela/Elabela/Toddler: New perspectives in molecular mechanism of heart failure

Background. Despite significant therapeutic advances, heart failure (HF) remains unacceptably high in morbidity and mortality. Additionally, its high-care and costs make HF a deadly and costly disease. First reported independently by two group of researchers, Apela/Elabela/Toddler (ELA) is the second endogenous apelin-receptor ligand discovered which is encoded from a previously classified non-coding gene, and has emerged as a key signalling-pathway in the cardiovascular system. Aims. To explore and summarise the biological effects and diagnostic potential of ELA as a new biomarker for heart failure. Results. ELA (prepro-ELA 54 AA) is a molecule with three isoforms (ELA 11,16 and 32), recently identified as the second endogenous ligand to APJ-receptor and functions to mediate early cardiac development during zebrafish embryogenesis by inducing cardiogenesis, vasculogenesis and bone formation. In adults, it enhances cardiac contractility, promotes vasodilatory effects, mediates fluid homeostasis, reduces food intake, limits kidney dysfunction and exerts anti-atherosclerotic as well as anti-oxidative properties. Conclusion. These results show that ELA, an endogenous agonist of the APJ-receptor exerts cardiovascular effects comparable and potentially more potent than apelin and is found to be downregulated in experimental models and humans with heart failure.