Cardiovascular Research Center, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, China; Zhengzhou Sino-Crystal Diamond Co., Ltd., Zhengzhou, Henan 450001, China.
Cardiovascular Research Center, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, China.
Int Immunopharmacol. 2024 Dec 5;142(Pt B):113060. doi: 10.1016/j.intimp.2024.113060. Epub 2024 Sep 24.
One component of the polycomb repressor complex 2 is histone methyltransferase zeste homolog 2 (EZH2), which is also called Enhancer of zeste homolog 2. It is considered a potential therapeutic target for inhibiting endothelial dysfunction.. Hence, directing efforts towards EZH2 to weaken endothelium damage and regulate vascular lesions proves to be a highly successful therapeutic approach for enhancing endothelial dysfunction. This study aimed to investigate the mechanism by which salidroside (SAL) improves hydrogen peroxide (HO)-induced endothelial dysfunction. The investigation involved the use of many techniques, including western blotting, real-time polymerase chain reaction (RT-PCR), a scratch test, molecular docking, and other methods. The experimental findings demonstrated that SAL has the ability to inhibit the impaired functioning of endothelial cells caused by HO and decrease the levels of NF-κB p65, NLRP3, TNF-α, Beclin1, LC3, and P62 proteins. Additionally, there seems to be a targeting relationship between SAL and EZH2, and EZH2 knockdown can reproduce the protective effect of SAL on endothelial function. Overall, SAL inhibits HO-induced HUVEC dysfunction by regulating autophagy and inflammatory signaling pathways through EZH2.
多梳抑制复合物 2 的一个组成部分是组蛋白甲基转移酶 zeste 同源物 2（EZH2），也称为 Enhancer of zeste 同源物 2。它被认为是抑制内皮功能障碍的潜在治疗靶点。因此，针对 EZH2 的努力被证明是一种非常成功的治疗方法，可以减弱内皮损伤并调节血管病变，从而增强内皮功能障碍。本研究旨在探讨红景天苷（SAL）改善过氧化氢（HO）诱导的内皮功能障碍的机制。该研究采用了多种技术，包括 Western blot、实时聚合酶链反应（RT-PCR）、划痕试验、分子对接等方法。实验结果表明，SAL 能够抑制 HO 引起的内皮细胞功能障碍，并降低 NF-κB p65、NLRP3、TNF-α、Beclin1、LC3 和 P62 蛋白的水平。此外，SAL 和 EZH2 之间似乎存在靶向关系，EZH2 敲低可以再现 SAL 对内皮功能的保护作用。总的来说，SAL 通过调节自噬和炎症信号通路来抑制 HO 诱导的 HUVEC 功能障碍，其作用靶点是 EZH2。
