Atherosclerosis (AS) is one of the significant chronic inflammatory pathology considering public health impact. Up-regulation of HDAC1 has been proved to be related with endothelial dysfunction which is correlated intimately with AS. Our research aims to investigate how histone deacetylase 1 (HDAC1)/miR-182-5p/vav guanine nucleotide exchange factor 3 (VAV3)/AKT axis participates in AS in terms of molecular mechanism. We detected miR-181-5p in human umbilical vein endothelial cells after treatment with aorta and ox-LDL in AS model mice. Dual luciferase reporter assay was employed to verify interaction of miR-182-5p and VAV3. ChIP was performed to determine the relationship between HDAC1 and promoter of miR-182-5p. Protein levels of HADC1, VAV3, AKT, p-AKT, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein 1 (MCP-1) were detected by western blot analysis. CCK8 and flow cytometry were used to detect cell viability and apoptosis, respectively. After different treatments, the ability of cells to form monoclonal cells was detected, and AS was evaluated by detecting arterial injury and inflammation-related factors. Overexpression of HDAC1 could inhibit HUVECs proliferation and promote AS in mouse model. It was verified by dual luciferase assay that miR-182-5p could bind to VAV3 3′UTR mRNA. Meanwhile, HDAC1 repressed miR-182-5p expression through binding to miR-182-5p promoter and then inhibit VAV3 expression further. In summary, HDAC1 promoted AS through AKT pathway, which was improved by VAV3 activation mediated by miR-182-5p. Our results demonstrated that HDAC1 repressed miR-182-5p and activating AKT pathway via improving VAV3 to promote AS progression.

考虑到公共卫生影响，动脉粥样硬化 (AS) 是一种重要的慢性炎症病理。已证明 HDAC1 的上调与内皮功能障碍有关，而内皮功能障碍与 AS 密切相关。我们的研究旨在探讨组蛋白去乙酰化酶 1 (HDAC1)/miR-182-5p/vav 鸟嘌呤核苷酸交换因子 3 (VAV3)/AKT 轴如何从分子机制方面参与 AS。我们在 AS 模型小鼠的主动脉和 ox-LDL 治疗后检测到人脐静脉内皮细胞中的 miR-181-5p。双荧光素酶报告基因检测用于验证 miR-182-5p 和 VAV3 的相互作用。进行 ChIP 以确定 HDAC1 与 miR-182-5p 启动子之间的关系。HADC1、VAV3、AKT、p-AKT、血管细胞粘附分子-1 (VCAM-1)、细胞间细胞粘附分子-1 (ICAM-1)、通过蛋白质印迹分析检测到单核细胞趋化蛋白1（MCP-1）和单核细胞趋化蛋白1（MCP-1）。CCK8和流式细胞术分别用于检测细胞活力和凋亡。不同处理后检测细胞形成单克隆细胞的能力，通过检测动脉损伤和炎症相关因素评价AS。HDAC1的过表达可以抑制HUVECs增殖并促进小鼠模型中的AS。双荧光素酶测定证实miR-182-5p可以与VAV3 3'UTR mRNA结合。同时，HDAC1通过与miR-182-5p启动子结合来抑制miR-182-5p的表达，进而进一步抑制VAV3的表达。总之，HDAC1 通过 AKT 通路促进 AS，通过 miR-182-5p 介导的 VAV3 激活得到改善。