Sunjaya Anthony P, Sunjaya Angela F, Ferdinal Frans
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tarumanagara University, Jl. Letjen S. Parman No. 1, Jakarta, Indonesia.
Glob Cardiol Sci Pract. 2019 Sep 20;2019(2):e201915. doi: 10.21542/gcsp.2019.15.
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. To explore and summarise the biological effects and diagnostic potential of ELA as a new biomarker for heart failure. 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. 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.
尽管在治疗方面取得了重大进展，但心力衰竭（HF）的发病率和死亡率仍然高得令人无法接受。此外，其高昂的护理需求和成本使HF成为一种致命且代价高昂的疾病。Apela/Elabela/Toddler（ELA）由两组研究人员分别首次报道，是发现的第二种内源性apelin受体配体，由一个先前分类为非编码基因编码，已成为心血管系统中的关键信号通路。为了探索和总结ELA作为心力衰竭新生物标志物的生物学效应和诊断潜力。ELA（前体-ELA 54个氨基酸）是一种具有三种异构体（ELA 11、16和32）的分子，最近被确定为APJ受体的第二种内源性配体，在斑马鱼胚胎发育过程中通过诱导心脏发生、血管生成和骨形成来介导早期心脏发育。在成体中，它增强心脏收缩力，促进血管舒张作用，介导液体稳态，减少食物摄入，限制肾功能障碍，并具有抗动脉粥样硬化和抗氧化特性。这些结果表明，ELA作为APJ受体的内源性激动剂，发挥的心血管效应与apelin相当，甚至可能更强，并且在心力衰竭的实验模型和人类中被发现表达下调。
