Endothelial dysfunction (ED) has a high incidence in chronic kidney disease (CKD) and is identified as a precursor to cardiovascular events. Recent studies suggest that leptin may be the missing link between ED and CKD. The objective of this study was to investigate the mechanism by which leptin causes ED and the connection with leptin and indicators of ED in CKD patients. Analysis of leptin-treated human umbilical vein endothelial cells (HUVECs) showed increased expression of interleukin 6 (IL-6), endothelin 1 (ET-1) and human monocyte chemoattractant protein 1 (MCP-1), resulting in F-actin recombination and vinculin aggregation as well as endothelial cell migration. In vitro studies have shown that leptin leads to increased WNT1 expression and the accumulation of β-catenin. Metastasis-associated protein 1 (MTA1), a critical upstream modifier of WNT1 signaling, increased the expression level in leptin-mediated regulation. In contrast, opposite results were observed when cells are transfected with MTA1 or WNT1 shRNA lentivirus vectors. Among 160 patients with CKD and 160 healthy subjects, patients with CKD had significantly higher serum leptin levels than those of the control group, which were positively correlated with increased levels of IL-6, ET-1 and MCP-1. However, these levels were negatively correlated with flow-mediated dilatation (FMD). Hence, these investigations provided novel information on the increased serum leptin levels in CKD patients leading to ED via the MTA1-WNT/β-catenin pathway.

内皮功能障碍 (ED) 在慢性肾脏病 (CKD) 中发病率很高，并被认为是心血管事件的先兆。最近的研究表明，瘦素可能是 ED 和 CKD 之间缺失的环节。本研究的目的是探讨瘦素引起 ED 的机制以及瘦素与 CKD 患者 ED 指标的关系。对瘦素处理的人脐静脉内皮细胞 (HUVEC) 的分析显示，白细胞介素 6 (IL-6)、内皮素 1 (ET-1) 和人单核细胞趋化蛋白 1 (MCP-1) 的表达增加，导致 F-肌动蛋白重组和纽蛋白聚集以及内皮细胞迁移。体外研究表明，瘦素会导致 WNT1 表达增加和 β-catenin 积累。转移相关蛋白 1 (MTA1) 是 WNT1 信号传导的关键上游调节剂，可增加瘦素介导的调节中的表达水平。相反，当细胞用MTA1或WNT1 shRNA慢病毒载体转染时，观察到相反的结果。在160名CKD患者和160名健康受试者中，CKD患者血清瘦素水平显着高于对照组，且与IL-6、ET-1和MCP-1水平升高呈正相关。然而，这些水平与血流介导的扩张（FMD）呈负相关。因此，这些研究提供了有关 CKD 患者血清瘦素水平升高通过 MTA1-WNT/β-连环蛋白途径导致 ED 的新信息。