Atherosclerosis is the common vascular disease. Vascular smooth muscle cell proliferation and vascular endothelial cell (VEC) dysfunction are involved in the causes of atherosclerosis. And oxidized low-density lipoprotein (ox-LDL)-induced vascular endothelial cells (VECs) are suitable models for studying atherosclerosis development. Paeonol was reported to repress ox-LDL-induced VEC progression. However, its detailed mechanism was not fully reported. MicroRNAs (miRNAs) acted as regulators in multiple diseases. Previous findings found that microRNA-338-3p (miR-338-3p) was overexpressed in Atherosclerosis process. However, the function and underlying mechanism of miR-338-3p in ox-LDL-treated VECs needed to be elucidated. The purpose of this research was to reveal the role of miR-338-3p in paeonol-regulated ox-LDL-induced VEC progression. Cell counting kit-8 (CCK-8) and flow cytometry were employed to determine cell viability and apoptosis, respectively. Moreover, the levels of IL-6 and IL-1β were analyzed using enzyme-linked immunosorbent assay, as well as the contents of reactive oxygen species, lactate dehydrogenase, and malonic dialdehyde were investigated using related kits. Furthermore, quantitative real-time polymerase chain reaction was carried out to determine the expression of miR-338-3p. Western blot assay was conducted to detect the level of tet methylcytosine dioxygenase 2 (TET2). Besides, the interaction between miR-338-3p and TET2 was predicted by DIANA, and then confirmed by the dual-luciferase reporter assay and RNA immunoprecipitation assay. Ox-LDL repressed mice VEC viability, and promoted apoptosis, inflammatory response, and oxidative injury. Paeonol inhibited the effect of ox-LDL on the growth of the VECs. Furthermore, paeonol regulated VEC development via downregulating miR-338-3p expression. Interestingly, miR-338-3p targeted TET2 and inhibited TET2 expression. MiR-338-3p modulated ox-LDL-treated VEC growth through suppressing TET2 expression. We demonstrated that paeonol attenuated the effect of ox-LDL on the development of mice VECs via modulating miR-338-3p/TET2 axis, providing a theoretical basis for the treatment of AS.

动脉粥样硬化是常见的血管疾病。血管平滑肌细胞增殖和血管内皮细胞 (VEC) 功能障碍与动脉粥样硬化的原因有关。氧化低密度脂蛋白 (ox-LDL) 诱导的血管内皮细胞 (VEC) 是研究动脉粥样硬化发展的合适模型。据报道，丹皮酚可抑制 ox-LDL 诱导的 VEC 进展。然而，其详细机制尚未完全报道。MicroRNAs (miRNAs) 在多种疾病中充当调节剂。先前的研究发现，microRNA-338-3p (miR-338-3p) 在动脉粥样硬化过程中过度表达。然而，需要阐明 miR-338-3p 在 ox-LDL 处理的 VEC 中的功能和潜在机制。本研究的目的是揭示 miR-338-3p 在丹皮酚调节的 ox-LDL 诱导的 VEC 进展中的作用。细胞计数试剂盒-8 (CCK-8) 和流式细胞术分别用于测定细胞活力和凋亡。此外，使用酶联免疫吸附法分析了 IL-6 和 IL-1β 的水平，并使用相关试剂盒研究了活性氧、乳酸脱氢酶和丙二醛的含量。此外，进行定量实时聚合酶链反应以确定 miR-338-3p 的表达。进行蛋白质印迹测定以检测tet甲基胞嘧啶双加氧酶2（TET2）的水平。此外，miR-338-3p 和 TET2 之间的相互作用由 DIANA 预测，然后通过双荧光素酶报告基因测定和 RNA 免疫沉淀测定证实。Ox-LDL 抑制小鼠 VEC 活力，并促进细胞凋亡、炎症反应和氧化损伤。丹皮酚抑制 ox-LDL 对 VEC 生长的影响。此外，丹皮酚通过下调 miR-338-3p 表达来调节 VEC 的发展。有趣的是，miR-338-3p 靶向 TET2 并抑制 TET2 表达。MiR-338-3p 通过抑制 TET2 表达调节 ox-LDL 处理的 VEC 生长。我们证明丹皮酚通过调节miR-338-3p/TET2轴减弱ox-LDL对小鼠VECs发育的影响，为AS的治疗提供了理论依据。