Elabela(19-32) TFA is an endogenous agonist that binds to the apelin receptor (APJ) and activates the Gαi1 (EC50=8.6nM) and β-arrestin-2 (EC50=166nM) signaling pathways[1-2]. Elabela(19-32) TFA is primarily used to study the pathophysiological mechanisms of cardiovascular diseases such as hypertension and heart failure, and is a potential therapeutic agent for cardiovascular diseases[3-4].
In vitro, pretreatment of H9c2 cardiomyocytes with Elabela(19-32) TFA (5nM), followed by hypoxia/reoxygenation (H/R) treatment to simulate myocardial ischemia-reperfusion injury. Elabela(19-32) TFA significantly inhibits apoptosis, reduces the expression of fibrosis markers (type I/III collagen), and improves mitochondrial dysfunction[5]. Treatment of HUVECs and EA.hy926 cells with Elabela(19-32) TFA (0.01–5μmol/L) for 6 or 24 hours. Elabela(19-32) TFA significantly enhances cell viability, promotes cell migration, and increases tube formation capacity[6].
In vivo, intraperitoneal injection of Elabela(19-32) TFA (0.5mg/kg/day) for 28 days in endothelial-specific ELA knockout mice and wild-type mice with hindlimb ischemia (HLI) models. Elabela(19-32) TFA markedly improves post-ischemic perfusion recovery and capillary density in ELA knockout mice, while upregulating the expression of VEGFR2, p-VEGFR2, and p-AKT[7]. In C57BL/6 mice with acute doxorubicin (15mg/kg, single intraperitoneal injection)-induced cardiotoxicity, subcutaneous administration of Elabela(19-32) TFA (2mg/kg) twice daily for 5 days. Elabela(19-32) TFA significantly improves cardiac function (left ventricular ejection fraction and fractional shortening), reduces serum levels of cardiac troponin T and creatine kinase-MB isoenzyme, and attenuates the decline in heart weight/body weight ratio and cardiomyocyte atrophy[8].
References:
[1] Sharma M, Prabhavalkar KS, Bhatt LK. Elabela Peptide: An Emerging Target in Therapeutics. Curr Drug Targets. 2022;23(14):1304-1318.
[2] Eberlé D, Marousez L, Hanssens S, et al. Elabela and Apelin actions in healthy and pathological pregnancies. Cytokine Growth Factor Rev. 2019 Apr;46:45-53.
[3] Gao S, Chen H. Therapeutic potential of apelin and Elabela in cardiovascular disease. Biomed Pharmacother. 2023 Oct;166:115268.
[4] Xu C. Cardiovascular aspects of ELABELA: A potential diagnostic biomarker and therapeutic target. Vascul Pharmacol. 2023 Aug;151:107193.
[5] Yu P, Ma S, Dai X, et al. Elabela alleviates myocardial ischemia reperfusion-induced apoptosis, fibrosis and mitochondrial dysfunction through PI3K/AKT signaling. Am J Transl Res. 2020 Aug 15;12(8):4467-4477.
[6] Wang X, Liang G, Guo Q, et al. ELABELA improves endothelial cell function via the ELA-APJ axis by activating the PI3K/Akt signalling pathway in HUVECs and EA.hy926 cells. Clin Exp Pharmacol Physiol. 2020 Dec;47(12):1953-1964.
[7] Peng JY, Fu X, Luo XY, et al. Endothelial ELABELA improves post-ischemic angiogenesis by upregulating VEGFR2 expression. Transl Res. 2024 Aug;270:13-23.
[8] Chen D, Yu W, Zhong C, et al. Elabela ameliorates doxorubicin-induced cardiotoxicity by promoting autophagic flux through TFEB pathway. Pharmacol Res. 2022 Apr;178:106186.
Elabela(19-32) TFA是一种与apelin受体（APJ）结合的内源性激动剂，能够激活Gαi1（EC50=8.6nM）和β-arrestin-2（EC50=166nM）信号通路[1-2]。Elabela(19-32) TFA多用于研究高血压、心力衰竭等心血管疾病的病理生理的机制，是潜在的心血管疾病治疗药物[3-4]。
在体外，Elabela(19-32) TFA（5nM）预处理H9c2心肌细胞，随后以缺氧/复氧（H/R）处理模拟心肌缺血再灌注损伤。Elabela(19-32) TFA显著抑制细胞凋亡、减轻纤维化标志物（I/III型胶原）表达、改善线粒体功能障碍[5]。Elabela(19-32) TFA（0.01–5μmol/L）处理HUVECs和EA.hy926细胞6或24小时，Elabela(19-32) TFA显著增强细胞活力、促进细胞迁移并提高管形成能力[6]。
在体内，Elabela(19-32) TFA（0.5mg/kg/day）腹腔注射28天，用于处理后肢缺血（HLI）模型的内皮特异性ELA敲除小鼠和野生型小鼠，显著改善了ELA敲除小鼠的缺血后灌注恢复和毛细血管密度，并上调了VEGFR2、p-VEGFR2和p-AKT的表达[7]。Elabela(19-32) TFA（2mg/kg）每日两次皮下注射，用于处理单次腹腔注射多柔比星（15mg/kg）诱导的急性心脏毒性C57BL小鼠模型，持续5天。Elabela(19-32) TFA显著改善了心脏功能（左心室射血分数和短轴缩短率），降低了血清心肌肌钙蛋白T和肌酸激酶同工酶水平，减轻了心脏重量/体重比值的下降和心肌细胞萎缩[8]。