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Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis

Author

Listed:
  • Yongmei Liu

    (Wake Forest School of Medicine)

  • Lindsay M. Reynolds

    (Wake Forest School of Medicine)

  • Jingzhong Ding

    (Wake Forest School of Medicine)

  • Li Hou

    (Wake Forest School of Medicine)

  • Kurt Lohman

    (Wake Forest School of Medicine)

  • Tracey Young

    (Wake Forest School of Medicine)

  • Wei Cui

    (Wake Forest School of Medicine)

  • Zhiqing Huang

    (Duke University)

  • Carole Grenier

    (Duke University)

  • Ma Wan

    (National Institutes of Health)

  • Hendrik G. Stunnenberg

    (Nijmegen Centre for Molecular Life Sciences (NCMLS))

  • David Siscovick

    (New York Academy of Medicine)

  • Lifang Hou

    (Northwestern University Feinberg School of Medicine)

  • Bruce M. Psaty

    (University of Washington
    Kaiser Permanente Washington Health Research Institute)

  • Stephen S. Rich

    (University of Virginia)

  • Jerome I. Rotter

    (Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center)

  • Joel D. Kaufman

    (University of Washington)

  • Gregory L. Burke

    (Wake Forest School of Medicine)

  • Susan Murphy

    (Duke University)

  • David R. Jacobs

    (University of Minnesota)

  • Wendy Post

    (Johns Hopkins University)

  • Ina Hoeschele

    (Biocomplexity Institute and Department of Statistics)

  • Douglas A. Bell

    (National Institutes of Health)

  • David Herrington

    (Wake Forest School of Medicine)

  • John S. Parks

    (Wake Forest School of Medicine)

  • Russell P. Tracy

    (University of Vermont)

  • Charles E. McCall

    (Wake Forest School of Medicine)

  • James H. Stein

    (University of Wisconsin School of Medicine and Public Health)

Abstract

Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator, ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development. ARID5B CpG (cg25953130) methylation is inversely associated with both ARID5B expression and atherosclerosis, consistent with this CpG residing in an ARID5B enhancer region, based on chromatin capture and histone marks data. Mediation analysis supports assumptions that ARID5B expression mediates effects of cg25953130 methylation and several cardiovascular disease risk factors on atherosclerotic burden. In lipopolysaccharide-stimulated human THP1 monocytes, ARID5B knockdown reduced expression of genes involved in atherosclerosis-related inflammatory and lipid metabolism pathways, and inhibited cell migration and phagocytosis. These data suggest that ARID5B expression, possibly regulated by an epigenetically controlled enhancer, promotes atherosclerosis by dysregulating immunometabolism towards a chronic inflammatory phenotype.

Suggested Citation

  • Yongmei Liu & Lindsay M. Reynolds & Jingzhong Ding & Li Hou & Kurt Lohman & Tracey Young & Wei Cui & Zhiqing Huang & Carole Grenier & Ma Wan & Hendrik G. Stunnenberg & David Siscovick & Lifang Hou & B, 2017. "Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00517-4
    DOI: 10.1038/s41467-017-00517-4
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