Elabela-APJ轴调控Akt/Sox17信号在高血压血管内皮损伤及功能紊乱中的作用及机制研究

高血压严重危害人类健康，与血管内皮损伤及功能紊乱密切相关。前期研究工作我们运用脉搏波传导速度检测血管功能（Advanced Materials，2017），同时我们观察到Apelin具有一定的降压和心血管保护作用。Elabela（ELA）是近年来发现的Apelin受体（APJ）的新型内源性配体，主要在血管内皮细胞表达，能调节血压及血管功能，但其对高血压介导的血管内皮损伤及功能紊乱是否有调控作用尚不清楚。在此基础上，本课题拟分析高血压患者ELA、Apelin、APJ、Sox17与血管结构功能损伤的相关性；采用高血压模型动物和细胞进行体内外实验，探讨高血压状态下，血管内皮Akt/Sox17/eNOS信号、凋亡、氧化应激、炎症反应及内皮功能的改变及ELA干扰对其调控作用和机制，以阐明ELA-APJ轴保护内皮细胞功能的机制，为高血压血管损伤早期防治找到新靶点。

Hypertension is seriously harmful to human health and is closely related to vascular endothelial injury and dysfunction. In the preliminary study, we used pulse wave velocity to detect vascular function (Advanced Materials, 2017), and we observed that Apelin had certain hypotensive and cardiovascular protective effects. Elabela (ELA) was found as a new type of endogenous ligand of Apelin receptor (APJ) in recent years, which mainly expressed in vascular endothelial cells. ELA could regulate blood pressure and blood vessel function, but its role on the vascular endothelial injury and dysfunction of hypertension is not clear. Based on our previous findings, we are going to investigate the relationship among ELA, Apelin, APJ, Sox17 and vascular function in hypertensive patients. The aim of his study is to demonstrate the effect of ELA-APJ axis on blood pressure, endothelial Akt/Sox17/eNOS signal, apoptosis, oxidative stress and inflammation by using hypertensive animal model and cultured endothelial cells. The impact of ELA interference on its regulation function and mechanism is also discussed. This project is designed to clarify the mechanism of ELA in protecting hypertensive endothelial function. It is hopeful to find new targets for early prevention and treatment of hypertension.