Xiao L I, Cao Yu, Wang Yang, Lai Xin, Gao Ke-Qin, Du Pei, Zhang Bi-Kui, Jia Su-Jie
Pharmazie. 2018 Apr 2;73(4):202-206. doi: 10.1691/ph.2018.7342.
To investigate whether there are aberrant acetylation modifications in global histone and monocyte chemoattractant protein-1 (MCP-1) promoter in monocytes from patients with coronary artery disease (CAD) and demonstrate the potential mechanisms.
CD14+ monocytes were isolated from 13 patients with CAD and 18 confirmed non-CAD controls using magnetic beads. Global histone H3/H4 acetylation and H3K4/H3K27 tri-methylation levels were measured with enzyme-linked immunosorbent assay. Quantitative real time-PCR was performed to detect the mRNA expression levels of MCP-1 and enzymes involved in histone modification processes. Histone modification levels in MCP-1 promoter were assessed by ChIP-qPCR assay.
Our results showed a markedly lower global histone H3 acetylation level in monocytes from CAD patients. Global H3K27 tri-methylation level was significantly increased in monocytes from CAD patients. Furthermore, the mRNA expression levels of epigenetic modification enzymes HDAC3, SIRT1, P300, JMJD3 and SUV39H1 were decreased significantly in monocytes from CAD patients, while HDAC7 mRNA expression level was markedly increased. MCP-1 mRNA expression level was increased histone H3/H4 acetylation levels in MCP-1 promoter were markedly increased in monocytes of CAD patients.
Aberrant histone modifications, including acetylation and tri-methylation, were found both in global histone and specific MCP-1 gene locos in monocytes from patients with CAD. Aberrant epigenetic modification enzymes expressions may be the regulatory mechanism responsible for aberrant histone modifications.
研究冠心病（CAD）患者单核细胞中整体组蛋白和单核细胞趋化蛋白-1（MCP-1）启动子是否存在异常乙酰化修饰，并阐明潜在机制。
使用磁珠从13例CAD患者和18例确诊的非CAD对照者中分离CD14+单核细胞。采用酶联免疫吸附测定法检测整体组蛋白H3/H4乙酰化和H3K4/H3K27三甲基化水平。进行定量实时PCR以检测MCP-1及参与组蛋白修饰过程的酶的mRNA表达水平。通过染色质免疫沉淀定量PCR（ChIP-qPCR）测定法评估MCP-1启动子中的组蛋白修饰水平。
我们的结果显示，CAD患者单核细胞中整体组蛋白H3乙酰化水平明显较低。CAD患者单核细胞中整体H3K27三甲基化水平显著升高。此外，CAD患者单核细胞中表观遗传修饰酶HDAC3、SIRT1、P300、JMJD3和SUV39H1的mRNA表达水平显著降低，而HDAC7 mRNA表达水平明显升高。CAD患者单核细胞中MCP-1 mRNA表达水平升高，MCP-1启动子中的组蛋白H3/H4乙酰化水平明显升高。
在CAD患者单核细胞的整体组蛋白和特定MCP-1基因位点均发现了包括乙酰化和三甲基化在内的异常组蛋白修饰。异常的表观遗传修饰酶表达可能是导致异常组蛋白修饰的调控机制。
