SMAD7 methylation as a novel marker in atherosclerosis
SMAD7 methylation as a novel marker in atherosclerosis
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SMAD7 甲基化作为动脉粥样硬化的新型标志物
DOI：
10.1016/j.bbrc.2018.01.121
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发表时间：
2018-02-05
影响因子：
3.1
通讯作者：
Zhang, An'wen
中科院分区：
文献类型：
--
作者：
Wei, Lihua;Zhao, Shimei;Zhang, An'wen
动脉粥样硬化是一个复杂的过程，包括炎症，胶原基质的积累和异常的DNA甲基化。众所周知，SMAD7在纤维化和炎症中起着重要作用。近年来，增加的研究集中在DNA甲基化和动脉粥样硬化之间的联系上。当前的研究旨在研究某些特定基因的甲基化状态，重点是动脉粥样硬化中的SMAD7并阐明其关系。我们发现，与正常动脉壁相比，在动脉粥样硬化斑块中显着甲基化SMAD7表达，其启动子区域被显着甲基化。使用MALDI-TOF MS，分别相对于匹配的正常对照组，在CPG单元5.8.15.16处的SMAD7启动子的DNA甲基化水平增加。相关分析表明，CPG单元5.8.15.16的SMAD7启动子的平均DNA甲基化水平与同型半胱氨酸水平（r = 0.724，p <.001）和颈动脉斑块得分呈正相关（r = 0.790，p <.001）。 SMAD7启动子在人动脉粥样硬化斑块和动脉粥样硬化患者中都是高甲基化的，它们与同型半胱氨酸水平和颈动脉斑块评分呈正相关。因此，甲基化的SMAD7可能是一种新颖的预测标记和动脉粥样硬化的疗法靶标。 （c）2018 Elsevier Inc.保留所有权利。
Atherosclerosis is a complicated process comprising inflammation, accumulation of collagen matrix and aberrant DNA methylation. SMAD7 is known to play an important role in fibrosis and inflammation. In recent years, increasing research has concentrated on the connection between DNA methylation and atherosclerosis. The current study was designed to investigate methylation status of some specific gene with a focus on SMAD7 in atherosclerosis and elucidate their relationship. We found that SMAD7 expression was decreased and its promoter region was markedly methylated in atherosclerotic plaques when compared with normal artery walls. Using MALDI-TOF MS, increased DNA methylation levels of SMAD7 promoter at CpG unit 5.8.15.16 were found in peripheral blood of atherosclerosis patients relative to matched normal controls, respectively. Correlation analysis revealed that mean DNA methylation levels of SMAD7 promoter of CpG unit 5.8.15.16 were positively associated with homocysteine levels (r = 0.724, p < .001) and carotid plaque scores(r = 0.790, p < .001). SMAD7 promoter is hyper-methylated both in human atherosclerotic plaques and atherosclerosis patients, which is positively associated with homocysteine levels and carotid plaque scores. Thus, methylated SMAD7 may be a novel predicted marker and therapeutics target for atherosclerosis. (C) 2018 Elsevier Inc. All rights reserved.