ELABELA, an early endogenous ligand for the G protein-coupled receptor APJ (apelin peptide jejunum, apelin receptor), has been known as an important regulator in cardiovascular homeostasis and may be a novel therapeutic target for multiple cardiovascular diseases (CVDs). At the physiological level, ELABELA exhibits angiogenic and vasorelaxant effects and is essential for heart development. At the pathological level, circulating ELABELA levels may be a novel diagnostic biomarker for various CVDs. ELABELA peripherally displays antihypertensive, vascular-protective, and cardioprotective effects, whereas central administration of ELABELA elevated BP and caused cardiovascular remodeling. This review highlights the physiological and pathological roles of ELABELA in the cardiovascular system. Enhancement of the peripheral ELABELA may be a promising pharmacological therapeutic strategy for CVDs.
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| http://dx.doi.org/10.1016/j.vph.2023.107193 | DOI Listing |
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The potential of serum elabela levels as a marker of diabetic retinopathy: results from a pilot cross-sectional study.
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We describe a structural and functional study of the G protein-coupled apelin receptor, which binds two endogenous peptide ligands, apelin and Elabela/Toddler (ELA), to regulate cardiovascular development and function. Characterisation of naturally occurring apelin receptor variants from the UK Genomics England 100,000 Genomes Project, and AlphaFold2 modelling, identifies T89 as important in the ELA binding site, and R168 as forming extensive interactions with the C-termini of both peptides. Base editing to introduce an R/H168 variant into human stem cell-derived cardiomyocytes demonstrates that this residue is critical for receptor binding and function.
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