Xia Zhangyong, Gu Mingliang, Jia Xiaodong, Wang Xiaoting, Wu Chunxia, Guo Jiangwen, Zhang Liyong, Du Yifeng, Wang Jiyue
Department of Neurology Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, P.R. China.
Joint Laboratory for Translational Medicine Research, Beijing Institute of Genomics, Chinese Academy of Sciences & Liaocheng People's Hospital, CAS Key Laboratory of Genomic Science and Information Chinese Academy of Sciences, Beijing 100101, P.R. China.
Aging (Albany NY). 2018 Jun 13;10(6):1324-1337. doi: 10.18632/aging.101470.
Atherosclerosis (AS) is a multifactorial disease. Exploration of DNA methylation in regulating gene transcription in a cell type- and stage-specific manner will shed light on understanding the biological processes associated with plaque stability. We identified 174 up-regulated genes with hypo-methylation in the promoter, and 86 down-regulated genes with hyper-methylation in the promoter, in AS vs. healthy controls. Among them, high expression of signaling lymphocytic activation molecule 7 (SLAM7) was examined in carotid plaque vs. intact tissue, in advanced plaque vs. early atherosclerotic tissue, and SLAMF7 protein expressed significantly higher in the unstable plaques than that in the stable plaques, especially in the CD68-positive macrophages. Depletion of SLAMF7 in plaque-derived macrophages induced a suppressed secretion of proinflammatory cytokines, and inhibited proliferation of vascular smooth muscle cells. These data provide emerging evidence that SLAMF7 could be a target of potential therapeutic intervention in carotid AS.
动脉粥样硬化（AS）是一种多因素疾病。以细胞类型和阶段特异性方式探索DNA甲基化在调节基因转录中的作用，将有助于理解与斑块稳定性相关的生物学过程。与健康对照相比，我们在AS中鉴定出174个启动子低甲基化的上调基因和86个启动子高甲基化的下调基因。其中，在颈动脉斑块与完整组织、晚期斑块与早期动脉粥样硬化组织中检测到信号淋巴细胞激活分子7（SLAM7）的高表达，并且SLAMF7蛋白在不稳定斑块中的表达明显高于稳定斑块，尤其是在CD68阳性巨噬细胞中。斑块来源的巨噬细胞中SLAMF7的缺失导致促炎细胞因子分泌受抑制，并抑制血管平滑肌细胞的增殖。这些数据提供了新的证据，表明SLAMF7可能是颈动脉AS潜在治疗干预的靶点。
