Department of Circulatory, Affiliated Center of Shenyang Medical College, Shenyang, Liaoning, China.
Central Laboratory of Affiliated Hospital of Shenyang Medical College, Shenyang, Liaoning, China.
Biomed Res Int. 2022 Jul 30;2022:7408136. doi: 10.1155/2022/7408136. eCollection 2022.
Atherosclerosis is a chronic inflammatory response mediated by various factors, where epigenetic regulation involving histone deacetylation is envisaged to modulate the expression of related proteins by regulating the binding of transcription factors to DNA, thereby influencing the development of atherosclerosis. The mechanism of atherosclerosis by histone deacetylation is partly known; hence, this project aimed at investigating the role of histone deacetylase 9 (HDAC9) in atherosclerosis. For this purpose, serum was separated from blood samples following clotting and centrifugation from atherosclerotic and healthy patients ( = 40 each), and then, various tests were performed. The results indicated that toll-like receptor 4 (TLR4) was not only positively correlated to the HDAC9 gene, but was also upregulated in atherosclerosis, where it was also significantly upregulated in the atherosclerosis cell model of oxidized low-density lipoprotein-induced macrophages. Conversely, the TLR4 was significantly downregulated in instances of loss of HDAC9 function, cementing the bridging relationship between HDAC9 and macrophage polarization, where the HDAC9 was found to upregulate M1 macrophage polarization which translated into the release of higher content of proinflammatory cytokines such as interleukin-1beta (IL-1) and tumor necrosis factor-alpha (TNF-), which tend to significantly decrease following the deletion of TLR4. Hence, this study reports novel relation between epigenetic control and atherosclerosis, which could partly be explained by histone deacetylation.
动脉粥样硬化是一种由多种因素介导的慢性炎症反应，其中涉及组蛋白去乙酰化的表观遗传调控被认为可以通过调节转录因子与 DNA 的结合来调节相关蛋白的表达，从而影响动脉粥样硬化的发展。组蛋白去乙酰化在动脉粥样硬化中的作用机制部分已知；因此，本项目旨在研究组蛋白去乙酰化酶 9（HDAC9）在动脉粥样硬化中的作用。为此，从动脉粥样硬化和健康患者的血液样本中（= 40 例）凝血和离心后分离血清，然后进行各种测试。结果表明，Toll 样受体 4（TLR4）不仅与 HDAC9 基因呈正相关，而且在动脉粥样硬化中也上调，在氧化低密度脂蛋白诱导的巨噬细胞动脉粥样硬化细胞模型中也显著上调。相反，TLR4 在 HDAC9 功能丧失的情况下显著下调，这巩固了 HDAC9 与巨噬细胞极化之间的桥接关系，发现 HDAC9 上调 M1 巨噬细胞极化，导致促炎细胞因子如白细胞介素 1β（IL-1）和肿瘤坏死因子-α（TNF-α）的释放含量更高，而 TLR4 缺失后这些细胞因子的释放量显著降低。因此，本研究报道了表观遗传调控与动脉粥样硬化之间的新关系，部分可以通过组蛋白去乙酰化来解释。
