Panhistone deacetylase inhibitors inhibit proinflammatory signaling pathways to ameliorate interleukin-18-induced cardiac hypertrophy

Gipsy Majumdar, Robert Rooney, I. Maria Johnson, Rajendra Raghow

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

We investigated the genome-wide consequences of pan-histone deacetylase inhibitors (HDACIs) trichostatin A (TSA) and m-carboxycinnamic acid bis-hydroxamide (CBHA) in the hearts of BALB/c mice eliciting hypertrophy in response to interleukin-18 (IL-18). Both TSA and CBHA profoundly altered cardiac chromatin structure that occurred concomitantly with normalization of IL-18-induced gene expression and amelioration of cardiac hypertrophy. The hearts of mice exposed to IL-18 +/- TSA or CBHA elicited distinct gene expression profiles. Of 184 genes that were differentially regulated by IL-18 and TSA, 33 were regulated in an opposite manner. The hearts of mice treated with IL-18 and/or CBHA elicited 147 differentially expressed genes (DEGs), a third of which were oppositely regulated by IL-18 and CBHA. Ingenuity Pathways and Kyoto Encyclopedia of Genes and Genomes analyses of DEGs showed that IL-18 impinged on TNF-α-and IFNγ-specific gene networks relegated to controlling immunity and inflammation, cardiac metabolism and energetics, and cell proliferation and apoptosis. These TNF-α- and IFNγ-specific gene networks, extensively connected with PI3K, MAPK, and NF-κB signaling pathways, were oppositely regulated by IL-18 and pan-HDACIs. Evidently, both TSA and CBHA caused a two- to fourfold induction of phosphatase and tensin homolog expression to counteract IL-18-induced proinflammatory signaling and cardiac hypertrophy.

Original languageEnglish (US)
Pages (from-to)1319-1333
Number of pages15
JournalPhysiological genomics
Volume43
Issue number24
DOIs
StatePublished - Dec 1 2011

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Interleukin-18
Cardiomegaly
trichostatin A
Acids
Histone Deacetylase Inhibitors
Gene Regulatory Networks
Genes
Genome
Encyclopedias
Phosphatidylinositol 3-Kinases
Transcriptome
Phosphoric Monoester Hydrolases
Hypertrophy
Chromatin
Immunity
Cell Proliferation
Apoptosis
Inflammation
Gene Expression

All Science Journal Classification (ASJC) codes

  • Physiology
  • Genetics

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Panhistone deacetylase inhibitors inhibit proinflammatory signaling pathways to ameliorate interleukin-18-induced cardiac hypertrophy. / Majumdar, Gipsy; Rooney, Robert; Johnson, I. Maria; Raghow, Rajendra.

In: Physiological genomics, Vol. 43, No. 24, 01.12.2011, p. 1319-1333.

Research output: Contribution to journalArticle

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