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. Jacobs; Wendy Post; Ina Hoeschele; Douglas A. Bell; David Herrington; John S. Parks; Russell P. Tracy; Charles E. McCall; James H. Stein

doi:10.1038/s41467-017-00517-4

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

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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.

Originele taal-2	Engels
Artikelnummer	393
Tijdschrift	Nature Communications
Volume	8
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s41467-017-00517-4
Status	Gepubliceerd - 1 dec. 2017
Extern gepubliceerd	Ja

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10.1038/s41467-017-00517-4

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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), Artikel 393. https://doi.org/10.1038/s41467-017-00517-4

@article{f674b49544b247149eb2498875ed9091,

title = "Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis",

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.",

author = "Yongmei Liu and Reynolds, {Lindsay M.} and Jingzhong Ding and Li Hou and Kurt Lohman and Tracey Young and Wei Cui and Zhiqing Huang and Carole Grenier and Ma Wan and Stunnenberg, {Hendrik G.} and David Siscovick and Lifang Hou and Psaty, {Bruce M.} and Rich, {Stephen S.} and Rotter, {Jerome I.} and Kaufman, {Joel D.} and Burke, {Gregory L.} and Susan Murphy and Jacobs, {David R.} and Wendy Post and Ina Hoeschele and Bell, {Douglas A.} and David Herrington and Parks, {John S.} and Tracy, {Russell P.} and McCall, {Charles E.} and Stein, {James H.}",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41467-017-00517-4",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

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Liu, Y, Reynolds, LM, Ding, J, Hou, L, Lohman, K, Young, T, Cui, W, Huang, Z, Grenier, C, Wan, M, Stunnenberg, HG, Siscovick, D, Hou, L, Psaty, BM, Rich, SS, Rotter, JI, Kaufman, JD, Burke, GL, Murphy, S, Jacobs, DR, Post, W, Hoeschele, I, Bell, DA, Herrington, D, Parks, JS, Tracy, RP, McCall, CE & Stein, JH 2017, 'Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis', Nature Communications, vol. 8, nr. 1, 393. https://doi.org/10.1038/s41467-017-00517-4

TY - JOUR

T1 - Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis

AU - Liu, Yongmei

AU - Reynolds, Lindsay M.

AU - Ding, Jingzhong

AU - Hou, Li

AU - Lohman, Kurt

AU - Young, Tracey

AU - Cui, Wei

AU - Huang, Zhiqing

AU - Grenier, Carole

AU - Wan, Ma

AU - Stunnenberg, Hendrik G.

AU - Siscovick, David

AU - Hou, Lifang

AU - Psaty, Bruce M.

AU - Rich, Stephen S.

AU - Rotter, Jerome I.

AU - Kaufman, Joel D.

AU - Burke, Gregory L.

AU - Murphy, Susan

AU - Jacobs, David R.

AU - Post, Wendy

AU - Hoeschele, Ina

AU - Bell, Douglas A.

AU - Herrington, David

AU - Parks, John S.

AU - Tracy, Russell P.

AU - McCall, Charles E.

AU - Stein, James H.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-017-00517-4

DO - 10.1038/s41467-017-00517-4

M3 - Article

C2 - 28855511

AN - SCOPUS:85028529546

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 393

ER -

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

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