Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan; Department of Cardiology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Peptides. 2019 Jan;111:62-70. doi: 10.1016/j.peptides.2018.04.011. Epub 2018 Apr 21.
Apelin is an endogenous peptide ligand for the G protein-coupled receptor APJ/AGTRL1/APLNR and is widely expressed throughout human body. In adult hearts Apelin-APJ/Apelin receptor axis is potently inotropic, vasodilatory, and pro-angiogenic and thereby contributes to maintaining homeostasis in normal and pathological hearts. Apelin-APJ/Apelin receptor is also involved in heart development including endoderm differentiation, heart morphogenesis, and coronary vascular formation. APJ/Apelin receptor had been originally identified as an orphan receptor for its sequence similarity to Angiotensin II type 1 receptor, and it was later deorphanized by identification of Apelin in 1998. Both Apelin and Angiotensin II are substrates for Angiotensin converting enzyme 2 (ACE2), which degrades the peptides and thus negatively regulates their agonistic activities. Elabela/Toddler, which shares little sequence homology with Apelin, has been recently identified as a second endogenous APJ ligand. Elabela plays crucial roles in heart development and disease conditions presumably at time points or at areas of the heart different from Apelin. Apelin and Elabela seem to constitute a spatiotemporal double ligand system to control APJ/Apelin receptor signaling in the heart. These expanding knowledges of Apelin systems would further encourage therapeutic applications of Apelin, Elabela, or their synthetic derivatives for cardiovascular diseases.
Apelin 是一种内源性肽配体，作用于 G 蛋白偶联受体 APJ/AGTRL1/APLNR，广泛存在于人体中。在成年心脏中，Apelin-APJ/Apelin 受体轴具有强大的正性肌力、血管扩张和促血管生成作用，有助于维持正常和病理心脏的内稳态。Apelin-APJ/Apelin 受体还参与心脏发育，包括内胚层分化、心脏形态发生和冠状血管形成。APJ/Apelin 受体最初因其与血管紧张素 II 型 1 受体的序列相似而被鉴定为孤儿受体，后来在 1998 年发现 Apelin 后被去孤儿化。Apelin 和血管紧张素 II 都是血管紧张素转换酶 2 (ACE2) 的底物，ACE2 可降解这些肽，从而负调控它们的激动活性。Elabela/Toddler 与 Apelin 的序列同源性很小，最近被鉴定为第二个内源性 APJ 配体。Elabela 在心脏发育和疾病条件中发挥着至关重要的作用，推测其作用的时间点或心脏区域与 Apelin 不同。Apelin 和 Elabela 似乎构成了时空双配体系统，以控制心脏中的 APJ/Apelin 受体信号。这些关于 Apelin 系统的扩展知识将进一步鼓励 Apelin、Elabela 或其合成衍生物在心血管疾病中的治疗应用。
