Abstract:
The prognosis of patients with advanced arteriosclerosis is bleak due to the lack of understanding of arteriosclerosis. Epigenetics-based DNA methylation plays an important role in the pathogenesis of arteriosclerosis. Hence, we aimed to identify the epigenetics-related aberrantly methylated differentially expressed genes (AMDEGs) in arteriosclerosis. A gene expression dataset and DNA methylation dataset were downloaded from the Gene Expression Omnibus database, and AMDEGs were identified on the basis of the relationship between methylation and expression. Subsequently, the expression levels of candidate hub genes were detected in human peripheral blood mononuclear cells (PBMCs) from atherosclerotic patients and control subjects by RT-qPCR and Western blot. Lastly, the methylation level of the target gene was detected using the MassARRAY method. In the present study, the hypermethylated and downregulated genes were mainly involved in vascular smooth muscle contraction. The hypomethylated and upregulated genes were markedly associated with immune-inflammatory processes. Following validation, LMOD1 was identified as the target gene, which was hypermethylated and downregulated in arteriosclerosis. The methylation levels of CpG sites in LMOD1 promoter were detected to be elevated in the PBMCs of atherosclerotic patients. In conclusion, AMDEGs identified in the present study may assist in understanding the pathogenesis of arteriosclerosis. LMOD1 exhibits potential as a promising diagnostic and therapeutic biomarker for arteriosclerosis.
摘要:
由于缺乏对动脉硬化的了解,晚期动脉硬化患者的预后黯淡。基于表观遗传学的DNA甲基化在动脉硬化的发病机制中起重要作用。因此,我们旨在鉴定动脉硬化中与表观遗传学相关的异常甲基化差异表达基因(AMDEGs).基因表达数据集和DNA甲基化数据集从基因表达综合数据库下载,根据甲基化和表达之间的关系鉴定AMDEGs。随后,通过RT-qPCR和Westernblot检测动脉粥样硬化患者和对照组的人外周血单个核细胞(PBMC)中候选hub基因的表达水平.最后,使用MassARRAY方法检测目标基因的甲基化水平。在本研究中,高甲基化和下调基因主要参与血管平滑肌收缩。低甲基化和上调的基因与免疫炎症过程显着相关。验证后,LMOD1被确定为靶基因,在动脉硬化中高甲基化和下调。在动脉粥样硬化患者的PBMC中检测到LMOD1启动子中CpG位点的甲基化水平升高。总之,本研究中鉴定的AMDEGs可能有助于理解动脉硬化的发病机理。LMOD1显示出作为动脉硬化的有前途的诊断和治疗生物标志物的潜力。