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Research Paper|Volume 10, Issue 6|pp 1324—1337

Integrated DNA methylation and gene expression analysis identifies SLAMF7 as a key regulator of atherosclerosis

Zhangyong Xia1, Mingliang Gu2, Xiaodong Jia3, Xiaoting Wang4, Chunxia Wu5, Jiangwen Guo6, Liyong Zhang7, Yifeng Du8, Jiyue Wang7
  • 1Department of Neurology Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, P.R. China
  • 2Joint 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
  • 3Joint Laboratory for Translational Medicine Research, Beijing Institute of Genomics, Chinese Academy of Sciences and Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China
  • 4Taishan Medical University, Taian, Shandong 271016, P.R. China
  • 5Department of Ultrasonic Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, P.R. China
  • 6Deparment of Neurology Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China
  • 7Department of Neurosurgery Liaocheng People’s Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong 252000, PR China
  • 8Department of Neurology Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
Received: April 16, 2018Accepted: June 4, 2018Published: June 13, 2018
https://doi.org/10.18632/aging.101470

Copyright: © 2018 Xia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.