DNA methylation and hydroxymethylation are associated with the degree of coronary atherosclerosis in elderly patients with coronary heart disease
DNA methylation and hydroxymethylation are associated with the degree of coronary atherosclerosis in elderly patients with coronary heart disease
复制标题
DNA甲基化和羟甲基化与老年冠心病患者冠状动脉粥样硬化程度相关。
DOI：
10.1016/j.lfs.2019.03.021
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发表时间：
2019-05-01
期刊：
影响因子：
6.1
通讯作者：
Zhang, Dongying
中科院分区：
文献类型：
--
作者：
Jiang, Dan;Sun, Min;Zhang, Dongying
目的：DNA甲基化和羟甲基化与冠心病(CHD)和动脉粥样硬化(AS)的发生发展密切相关。5-甲基胞嘧啶(5-MC)和5-羟甲基胞嘧啶(5-HMC)分别用于评估DNA甲基化和羟甲基化水平。然而，与CHD相关的5-MC和5-HMC水平仍然存在争议。本研究旨在探讨老年冠心病患者外周血中5-MC和5-HMC水平与冠状动脉粥样硬化程度的关系。主要方法：采用双抗体夹心法和斑点印迹法检测44例CHD患者和42例正常对照组外周血中5-MC和5-HMC水平。免疫组织化学染色观察人主动脉组织中5-MC、5-HMC和TET2的表达。Gensini评分用于评价冠状动脉粥样硬化程度。主要发现：冠心病患者PBMC和人主动脉粥样硬化斑块中的5-MC和5-HMC水平均高于对照组和组织标本。冠心病组TET2表达较对照组显著上调，而DNMT1、DNMT3A及其他Tet基因表达均呈上升趋势。Spearman相关分析显示，5-MC、5-HMC水平与Gensini评分呈正相关。调整后5-MC和5-HMC被认为是冠心病的危险因素。意义：老年冠心病患者外周血单个核细胞DNA甲基化和羟甲基化水平显著升高，并与冠状动脉粥样硬化程度呈正相关。
Aims: DNA methylation and hydroxymethylation are significantly related to the occurrence and development of coronary heart disease (CHD) and atherosclerosis (AS). 5-Methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) are used to assess DNA methylation and hydroxymethylation levels, respectively. However, 5-mC and 5-hmC levels associated with CHD remain controversial. In the present study, we aimed to investigate the association of the peripheral blood levels of 5-mC and 5-hmC and the degree of coronary atherosclerosis in elderly CHD patients.Main methods: 5-mC and 5-hmC levels in peripheral blood mononuclear cells (PBMCs) were measured in 44 CHD patients and 42 matched control subjects by ELISA and dot blot analysis. Immunohistochemical staining was used to observe 5-mC, 5-hmC and TET2 expression in human aortic tissue. Gensini score was used to evaluate the degree of coronary atherosclerosis.Key findings: 5-mC and 5-hmC levels in PBMCs from CHD patients and in human aortic atherosclerosis plaque were both higher than those in control subjects and in tissue samples. TET2 expression was significantly upregulated in CHD patients compared with control subjects, while only an increasing trend in the expression of DNMT1, DNMT3A and all the other TET genes were found. Spearman correlation analysis demonstrated that 5-mC and 5-hmC levels were positively correlated with Gensini score. 5-mC and 5-hmC were considered as the risk factors for CHD after adjustment.Significance: DNA methylation and hydroxymethylation levels in PBMCs from elderly CHD patients were significantly increased, showing a positive correlation with the degree of coronary atherosclerosis.