Institute of Prevention and Treatment of Cardiovascular Diseases in Alpine Environment of Plateau, Characteristic Medical Center of the Chinese People's Armed Police Force, Tianjin, China.
Institute of Prevention and Treatment of Dermatosis in Alpine Environment of Plateau, Characteristic Medical Center of the Chinese People's Armed Police Force, Tianjin, China.
Clin Exp Pharmacol Physiol. 2020 Dec;47(12):1953-1964. doi: 10.1111/1440-1681.13382. Epub 2020 Aug 6.
Destruction of endothelial cells (ECs) function is involved in the structural and functional pathophysiological processes of preeclampsia (PE). Vascular endothelial injury may pre-exist for several years in women that develop PE and may pose increased risks for hypertension, coronary artery disease, and type-2 diabetes mellitus. Previous findings showed that Elabela (ELA), the endogenous ligand of the apelin (APJ) receptor expressed mainly on ECs, may play a protective role in early pregnancy and prevent PE. However, the exact functional role and molecular mechanisms of ELA are unclear. Here, we aimed to classify whether and how ELA improves EC function via the ELA-APJ axis. Two human umbilical vein endothelial cell (HUVEC) lines, namely HUVECs and EA.hy926, were treated with ELA, and then their cellular activities were studied by performing CCK-8 tests, scratch-wound analysis, and tube-formation assays. Doses of ELA exceeding 0.01 μmol/L markedly improved the cell viability, migration, and tube formation ability of HUVECs and EA.hy926 cells. Western blot analysis indicated that the above effects caused by ELA were related to upregulation of the APJ receptor and activation of PI3K/Akt signalling. Further verification tests were performed using the PI3K inhibitor wortmannin, and the results illustrated that inhibiting PI3K/Akt signalling blocked the positive effects of ELA on EC function and APJ receptor expression. Taken together, our findings indicate that ELA may alter EC function via the ELA-APJ axis and PI3K/Akt signalling and that ELA shows promise for use in endothelial dysfunction therapy for preventing and treating PE.
内皮细胞 (ECs) 功能的破坏与子痫前期 (PE) 的结构和功能病理生理过程有关。血管内皮损伤可能在几年前就存在于发展为 PE 的女性中，这可能会增加高血压、冠心病和 2 型糖尿病的风险。先前的研究结果表明，Elabela (ELA)，即主要在 ECs 上表达的 Apelin (APJ) 受体的内源性配体，可能在早期妊娠中发挥保护作用，预防 PE。然而，ELA 的确切功能作用和分子机制尚不清楚。在这里，我们旨在通过 ELA-APJ 轴来分类 ELA 是否以及如何改善 EC 功能。用 ELA 处理两条人脐静脉内皮细胞 (HUVEC) 系，即 HUVECs 和 EA.hy926，然后通过 CCK-8 试验、划痕试验和管形成试验研究细胞活性。超过 0.01 μmol/L 的 ELA 剂量可显著提高 HUVECs 和 EA.hy926 细胞的细胞活力、迁移和管形成能力。Western blot 分析表明，ELA 引起的上述作用与 APJ 受体的上调和 PI3K/Akt 信号通路的激活有关。进一步使用 PI3K 抑制剂 wortmannin 进行验证试验，结果表明，抑制 PI3K/Akt 信号通路阻断了 ELA 对 EC 功能和 APJ 受体表达的正向作用。总之，我们的研究结果表明，ELA 可能通过 ELA-APJ 轴和 PI3K/Akt 信号通路改变 EC 功能，ELA 有望用于内皮功能障碍治疗，以预防和治疗 PE。
