Histone deacetylase 9 represses cholesterol efflux and alternatively activated macrophages in atherosclerosis development

Qiang Cao, Shunxing Rong, Joyce J. Repa, Richard St Clair, John S. Parks, Nilamadhab Mishra

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

OBJECTIVE - Recent genome-wide association studies revealed that a genetic variant in the loci corresponding to histone deacetylase 9 (HDAC9) is associated with large vessel stroke. HDAC9 expression was upregulated in human atherosclerotic plaques in different arteries. The molecular mechanisms how HDAC9 might increase atherosclerosis is not clear. APPROACH AND RESULTS - In this study, we show that systemic and bone marrow cell deletion of HDAC9 decreased atherosclerosis in LDLr (low density lipoprotein receptor) mice with minimal effect on plasma lipid concentrations. HDAC9 deletion resulted upregulation of lipid homeostatic genes, downregulation of inflammatory genes, and polarization toward an M2 phenotype via increased accumulation of total acetylated H3 and H3K9 at the promoters of ABCA1 (ATP-binding cassette transporter), ABCG1, and PPAR-γ (peroxisome proliferator-activated receptor) in macrophages. CONCLUSIONS - We conclude that macrophage HDAC9 upregulation is atherogenic via suppression of cholesterol efflux and generation of alternatively activated macrophages in atherosclerosis.

Original languageEnglish (US)
Pages (from-to)1871-1879
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume34
Issue number9
DOIs
StatePublished - 2014

Fingerprint

Histone Deacetylases
Atherosclerosis
Macrophages
Cholesterol
Up-Regulation
Lipids
Peroxisome Proliferator-Activated Receptors
ATP-Binding Cassette Transporters
LDL Receptors
Genome-Wide Association Study
Atherosclerotic Plaques
Bone Marrow Cells
Genes
Down-Regulation
Arteries
Stroke
Phenotype

Keywords

  • atherosclerosis
  • epigenomics
  • histone deacetylases
  • histones
  • macrophages

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Histone deacetylase 9 represses cholesterol efflux and alternatively activated macrophages in atherosclerosis development. / Cao, Qiang; Rong, Shunxing; Repa, Joyce J.; Clair, Richard St; Parks, John S.; Mishra, Nilamadhab.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 34, No. 9, 2014, p. 1871-1879.

Research output: Contribution to journalArticle

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AU - Clair, Richard St

AU - Parks, John S.

AU - Mishra, Nilamadhab

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