心血管疾病治疗中Elabela-APJ轴的研究进展

王涛, 牛秀珑, 王晓静, 张晓宁, 石蕊

武警医学 ›› 2025, Vol. 36 ›› Issue (11) : 1008-1012.

PDF(925 KB)
PDF(925 KB)
武警医学 ›› 2025, Vol. 36 ›› Issue (11) : 1008-1012.
综述

心血管疾病治疗中Elabela-APJ轴的研究进展

  • 王涛, 牛秀珑, 王晓静, 张晓宁, 石蕊
作者信息 +
文章历史 +

摘要

血管紧张素受体AT1相关受体蛋白(APJ)及其新型内源性配体Elabela(ELA)在动物及人体内均广泛表达。近年发现,ELA-APJ轴在心血管系统的生长发育和心血管疾病(CVD)中发挥重要作用,本文就其对心血管系统的保护作用及相关机制进行综述,为探讨以ELA-APJ轴为干预靶点的CVD临床治疗提供依据。

关键词

ELA-APJ轴 / CVD / 高血压

引用本文

导出引用
王涛, 牛秀珑, 王晓静, 张晓宁, 石蕊. 心血管疾病治疗中Elabela-APJ轴的研究进展[J]. 武警医学. 2025, 36(11): 1008-1012
中图分类号: R541   

参考文献

[1] O’Dowd B F, Heiber M, Chan A, et al. A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11[J]. Gene, 1993, 136(1-2) :355-360.
[2] Wagenaar G T M, Moll G N. Advances in the therapeutic potentials of ligands of the apelin receptor APJ[J]. Eur J Pharmacol, 2025, 991:177302.
[3] Tatemoto K, Hosoya M, Habata Y, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor[J]. Biochem Biophys Res Commun, 1998, 251(2) :471-476.
[4] Chng S C, Ho L, Tian J, et al. ELABELA: a hormone essential for heart development signals via the apelin receptor[J]. Dev Cell, 2013, 27(6) :672-680.
[5] Pauli A, Norris M L, Valen E, et al. Toddler: an embryonic signal that promotes cell movement via apelin receptors[J]. Science, 2014, 343(6172) :1248636.
[6] 田清平, 齐永芬, 刘梅林, 等. 血管紧张素受体AT1相关受体蛋白新的配体——Elabela的生物学效应及与心血管疾病的关系[J].生理科学进展, 2021, 52(1) :23-27.
[7] Wang Z, Yu D, Wang M, et al. Elabela-apelin receptor signaling pathway is functional in mammalian systems[J]. Sci Rep, 2015, 5:8170.
[8] Cox C M, D’Agostino S L, Miller M K, et al. Apelin, the ligand for the endothelial G-protein-coupled receptor, APJ, is a potent angiogenic factor required for normal vascular development of the frog embryo[J]. Dev Biol, 2006, 296(1): 177-189.
[9] Respekta N, Pich K, Dawid M, et al. The apelinergic system: apelin, ELABELA and APJ action on cell apoptosis: anti-apoptotic or pro-apoptotic effect[J].Cells, 2022, 12(1):150.
[10] Murza A, Sainsily X, Coquerel D, et al. Discovery and structure-activity relationship of a bioactive fragment of ELABELA that modulates vascular and cardiac functions[J]. J Med Chem, 2016, 59(7): 2962-2972.
[11] Li L F, Zhou Q L, Li X X, et al. Elabela-APJ axis: a novel therapy target for cardiovascular diseases[J]. Acta Biochim Biophys Sin, 2017, 49(11): 1042-1043.
[12] Artas G, Ozturk S, Kuloglu T, et al. A novel candidate molecule in the pathological grading of gliomas: elabela[J]. Turk Neuro-surg, 2018, 28(6): 989-994.
[13] 毛慧玲, 王春梅, 张如敏, 等. Elabela/APJ信号的结构与功能研究进展[J]. 药学学报, 2019, 54(7): 1174-1178.
[14] Song J, Tang J, Zhang Z, et al. Targeting the elabela/apelin-apelin receptor axis as a novel therapeutic approach for hypertension[J]. Chin Med J (Engl), 2022, 135(9): 1019-1026.
[15] Xie H, Luo G, Zheng Y, et al. Lowered circulating apelin is significantly associated with an increased risk for hypertension: a Meta-analysis[J]. Clin Exp Hyperten, 2017, 39(5): 435-440.
[16] Li Y, Yang X, Ouyang S, et al. Declined circulating Elabela levels in patients with essential hypertension and its association with impaired vascular function: a preliminary study[J]. Clin Exp Hypertens, 2020,42(3): 239-243.
[17] 张小宇, 刘苑雅, 丘雨旻, 等. 原发性高血压患者循环Elabela水平下降及其与血管功能的关系[J]. 中华高血压杂志, 2020, 8(12): 1200-1204.
[18] Rozwadowski J, Borodzicz-Jazdzyk S, Czarzasta K, et al. A review of the roles of apelin and ELABELA peptide ligands in cardiovascular disease, including heart failure and hypertension[J]. Med Sci Monit, 2022, 28: e938112.
[19] Xu C, Wang F, Chen Y, et al. Elabela antagonizes intrarenal renin-angiotensin system to lower blood pressure and protects against renal injury[J]. Am J Physiol Renal Physiol, 2020, 318(5): F1122-F1135.
[20] Schreiber C A, Holditch S J, Generous A, et al. Sustained Elabela gene therapy in high-salt diet-induced hypertensive rats[J]. Curr Gene Ther, 2017, 16(5): 349-360.
[21] Sainsily X, Coquerel D, Giguère H, et al. Elabela protects spontaneously hypertensive rats from hypertension and cardiorenal dysfunctions exacerbated by dietary high-salt intake[J]. Front Pharmacol, 2021, 2: 709467.
[22] 孟丹心, 李益民, 美合日阿依·约麦尔, 等. Elabela活性片段ELA14在对比剂致大鼠肾小管上皮细胞凋亡中的作用机制[J]. 医学研究生学报, 2022, 35(8): 841-846.
[23] Yang H, Zhang X, Ding Y, et al. Elabela: negative regulation of ferroptosis in trophoblasts via the ferritinophagy pathway implicated in the pathogenesis of preeclampsia[J].Cells, 2022, 12(1): 99.
[24] Ho L, van Dijk M, Chye S T J, et al. ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice[J]. Science, 2017, 357(6352): 707-713.
[25] Li L, Zeng H, Hou X, et al. Myocardial injection of apelin-overexpressing bonemarrow cells improves cardiac repair via upregulation of Sirt3 after myocardialinfarction[J]. PLoS One, 2013. 8(9): e71041.
[26] Zhou L, Sun H, Cheng R, et al. ELABELA, as a potential diagnostic biomarkerof preeclampsia, regulates abnormally shallow placentation via APJ[J]. Am J Physiol Endocrinol Metab, 2019, 316(5): E773-E781.
[27] Georgiadou D, Boussata S, Ranzijn W, et al. Peptide hormone ELABELA enhances extravillous trophoblast differentiation, but placenta is not the major source of circulating ELABELA in pregnancy[J]. Sci Rep, 2019,9(1): 19077.
[28] 刘丹丹, 张诗茂, 周 辉, 等. Elabela/APJ在子痫前期胎盘组织中的表达及其临床意义[J].重庆医学, 2020, 49(21): 3619-3623,3629.
[29] Xu C.The Elabela in hypertension, cardiovascular disease, renal disease, and preeclampsia: an update[J].J Hypertens, 2021,39(1): 12-22.
[30] Panaitescu B, Romero R, Gomez N, et al. ELABELA plasma concentrations are increased in women with late-onset preeclampsia[J]. J MaternFetal Neonatal Med, 2020, 33(1): 5-15.
[31] 赵晨园, 孙 蓉, 王丽静, 等. ELABELA通过调控AKT信号通路影响滋养细胞侵袭的研究[J].中国计划生育和妇产科, 2022, 14(3): 105-109,115.
[32] Goetze J P, Rehfeld J F, Carlsen J, et al. Apelin:a new plasma marker of cardiopulmonary disease[J]. Regul Peptide, 2006, 133(1/2/3) :134-138.
[33] Yang P, Read C, Kuc R E, et al. Elabela/toddler is an endogenous agonist of the apelin APJ receptor in the adult cardiovascular system and exogenous administration of the peptide compensates for the downregulation of its expression in pulmonary arterial hypertension clinical perspective[J]. Circulation, 2017, 135(12): 1160-1173.
[34] Chandra S M, Razavi H, Kim J,et al. Disruption of the apelin-APJ system worsens hypoxia-induced pulmonary hypertension[J]. Arterioscler Thromb Vasc Biol, 2011, 31(4): 814-820.
[35] Perjés Á, Kilpiö T, Ulvila J, et al. Characterization of apela, a novel endogenous ligand of apelin receptor, in the adult heart[J]. Basic Res Cardiol, 2016, 111(1): 2.
[36] Hou J Y, Wu H, Li S M, et al. ELABELA promotes the migration and homing of bone marrow mesenchymal stem cells to myocardial injury sites through the ERK1/2/miR-299a-5p/Exo70 pathway[J]. Front Pharmacol, 2025, 16: 1541869.
[37] Rakhshan K, Azizi Y, Naderi N, et al. ELABELA(ELA)peptide exerts cardioprotection against myocardial infarction by targeting oxidative stress and the improvement of heart function[J]. Int J Pept Res Ther, 2019, 25(2): 613-621.
[38] Pazoki-Toroudi H, Amani H, Ajami M, et al. Targeting mTOR signaling by polyphenols: a new therapeutic target for ageing[J]. Ageing Res Rev, 2016, 31: 55-66.
[39] Dönmez Y, Acele A. Increased Elabela levels in the acute ST segment elevation myocardial infarction patients[J]. Medicine (Baltimore), 2019, 98(43): e17645.
[40] Rachwalik M, Lesków A, Matusiewicz M, et al. Assessment of levels of apelinergic system peptides in serum and epicardial adipose tissue in patients with multivessel coronary artery disease who underwent myocardial revascularisation[J]. Biomedicines, 2025, 13(4): 809.
[41] Liu C, Xiong J, Yi X, et al. Decreased plasma ELABELA level as a novel screening indicator for heart failure: a cohort and observational study[J]. Sci Rep, 2024, 14(1): 11333.
[42] Liu W, Yan J, Pan W, et al. Apelin/Elabela-APJ: a novel therapeutic target in the cardiovascular system[J]. Ann Transl Med, 2020, 8(5): 243.
[43] Sato T, Sato C, Kadowaki A, et al. ELABELA-APJ axis protects from pressure overload heart failure and angiotensin II-induced cardiac damage[J]. Cardiovasc Res, 2017, 113(7): 760-769.
[44] Deng C, Chen H, Yang N, et al. Apela regulates fluid homeostasis by binding to the APJ receptor to activate Gi signaling[J]. Biol Chem, 2015, 290(30): 18261-18268.
[45] Chen Y, Xu C. The interaction partners of (pro)renin receptor in the distal nephron[J]. Faseb J, 2020, 34(11): 14136-14149.
[46] Ma Z, Song J J, Martin S, et al. The Elabela-APJ axis: a promising therapeutic target for heart failure[J]. Heart Fail Rev, 2021, 26(5): 1249-1258.

PDF(925 KB)

Accesses

Citation

Detail

段落导航
相关文章

/