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

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dc.contributor.authorLiu, Yongmeien
dc.contributor.authorReynolds, Lindsay M.en
dc.contributor.authorDing, Jingzhongen
dc.contributor.authorHou, Lien
dc.contributor.authorLohman, Kurten
dc.contributor.authorYoung, Traceyen
dc.contributor.authorCui, Weien
dc.contributor.authorHuang, Zhiqingen
dc.contributor.authorGrenier, Caroleen
dc.contributor.authorWan, Maen
dc.contributor.authorStunnenberg, Hendrik G.en
dc.contributor.authorSiscovick, Daviden
dc.contributor.authorHou, Lifangen
dc.contributor.authorPsaty, Bruce M.en
dc.contributor.authorRich, Stephen S.en
dc.contributor.authorRotter, Jerome I.en
dc.contributor.authorKaufman, Joel D.en
dc.contributor.authorBurke, Gregory L.en
dc.contributor.authorMurphy, Susan F.en
dc.contributor.authorJacobs, David R. Jr.en
dc.contributor.authorPost, Wendyen
dc.contributor.authorHoeschele, Inaen
dc.contributor.authorBell, Douglas A.en
dc.contributor.authorHerrington, David M.en
dc.contributor.authorParks, John S.en
dc.contributor.authorTracy, Russell P.en
dc.contributor.authorMcCall, Charles E.en
dc.contributor.authorStein, James H.en
dc.contributor.departmentStatisticsen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2019-02-07T14:44:22Zen
dc.date.available2019-02-07T14:44:22Zen
dc.date.issued2017-08-30en
dc.description.abstractLittle 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.en
dc.description.notesThis research was supported by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169, and R01 HL 119962 from the National Heart, Lung, and Blood Institute. The MESA Epigenomics and Transcriptomics Studies were funded by R01HL101250, R01 DK103531-01, R01 DK103531, R01 AG054474, and R01 HL135009-01 to Wake Forest University Health Sciences. The research described in this publication was funded in part by the U.S. Environmental Protection Agency through RD831697 to the University of Washington (MESA Air); it has not been subjected to the Agency's required peer and policy review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred.en
dc.description.sponsorshipNational Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, R01 HL 119962]en
dc.description.sponsorshipU.S. Environmental Protection Agency [RD831697]en
dc.description.sponsorship[R01HL101250]en
dc.description.sponsorship[R01 DK103531-01]en
dc.description.sponsorship[R01 DK103531]en
dc.description.sponsorship[R01 AG054474]en
dc.description.sponsorship[R01 HL135009-01]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41467-017-00517-4en
dc.identifier.issn2041-1723en
dc.identifier.other393en
dc.identifier.pmid28855511en
dc.identifier.urihttp://hdl.handle.net/10919/87525en
dc.identifier.volume8en
dc.language.isoen_USen
dc.publisherSpringer Natureen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleBlood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosisen
dc.title.serialNature Communicationsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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