PKD Research Group, Laboratory of Pediatrics, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussell), Department of Nephrology, Laarbeeklaan 101, 1090 Brussels, Belgium.
Nephrol Dial Transplant. 2022 Nov 23;37(12):2314-2326. doi: 10.1093/ndt/gfab070.
The apelinergic system (AS) is a novel pleiotropic system with an essential role in renal and cardiovascular physiology and disease, including water homeostasis and blood pressure regulation. It consists of two highly conserved peptide ligands, apelin and apela, and a G-protein-coupled apelin receptor. The two ligands have many isoforms and a short half-life and exert both similar and divergent effects. Vasopressin, apelin and their receptors colocalize in hypothalamic regions essential for body fluid homeostasis and interact at the central and renal levels to regulate water homeostasis and diuresis in inverse directions. In addition, the AS and renin-angiotensin system interact both systemically and in the kidney, with implications for the cardiovascular system. A role for the AS in diverse pathological states, including disorders of sodium and water balance, hypertension, heart failure, pre-eclampsia, acute kidney injury, sepsis and diabetic nephropathy, has recently been reported. Furthermore, several metabolically stable apelin analogues have been developed, with potential applications in diverse diseases. We review here what is currently known about the physiological functions of the AS, focusing on renal, cardiovascular and metabolic homeostasis, and the role of the AS in associated diseases. We also describe several hurdles and research opportunities worthy of the attention of the nephrology community.
阿片素能系统（AS）是一个新型的多功能系统，在肾脏和心血管生理学和疾病中具有重要作用，包括水稳态和血压调节。它由两种高度保守的肽配体，阿片肽和阿片肽，以及一种 G 蛋白偶联的阿片素受体组成。这两种配体有许多亚型，半衰期短，具有相似和不同的作用。血管加压素、阿片肽及其受体在调节体液稳态的下丘脑区域中存在共定位，并在中枢和肾脏水平相互作用，以相反的方向调节水稳态和利尿。此外，AS 与肾素-血管紧张素系统在全身和肾脏中相互作用，对心血管系统有影响。AS 在多种病理状态中的作用，包括钠和水平衡紊乱、高血压、心力衰竭、子痫前期、急性肾损伤、败血症和糖尿病肾病，最近已经被报道。此外，已经开发了几种代谢稳定的阿片肽类似物，具有在多种疾病中的潜在应用。我们在这里回顾了目前已知的 AS 的生理功能，重点介绍了肾脏、心血管和代谢稳态，以及 AS 在相关疾病中的作用。我们还描述了几个值得肾脏病学社区关注的障碍和研究机会。
