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

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, Bruce M. Psaty, Stephen S. Rich, Jerome I. Rotter, Joel D. Kaufman, Gregory L. Burke, Susan Murphy, David R. JacobsWendy Post, Ina Hoeschele, Douglas A. Bell, David Herrington, John S. Parks, Russell P. Tracy, Charles E. McCall, James H. Stein

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number393
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Liu, Y., Reynolds, L. M., Ding, J., Hou, L., Lohman, K., Young, T., Cui, W., Huang, Z., Grenier, C., Wan, M., Stunnenberg, H. G., Siscovick, D., Hou, L., Psaty, B. M., Rich, S. S., Rotter, J. I., Kaufman, J. D., Burke, G. L., Murphy, S., ... Stein, J. H. (2017). Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis. Nature communications, 8(1), [393]. https://doi.org/10.1038/s41467-017-00517-4