Evidence map›Paper›PMID 25941940›Full record

ArticleEpigenetics2015

HDAC inhibition attenuates cardiac hypertrophy by acetylation and deacetylation of target genes.

Jenny Y Y Ooi, Natasha K Tuano, Haloom Rafehi, Xiao-Ming Gao, Mark Ziemann, Xiao-Jun Du, Assam El-Osta

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 141 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. [PINK1 suppresses colorectal cancer cell growth through epigenetic regulation of histone modifications].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025
    Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Using Omics to Identify Novel Therapeutic Targets in Heart Failure.Circulation. Genomic and precision medicine · 2024
    Review
  11. Fibroblast Diversity and Epigenetic Regulation in Cardiac Fibrosis.International journal of molecular sciences · 2024
    Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 3 countries.

Jenny Y Y Ooia Epigenetics in Human Health and Disease Laboratory; Baker IDI Heart and Diabetes Institute ; Melbourne , Victoria , Australia.
Natasha K Tuano
Haloom Rafehi
Xiao-Ming Gao
Mark Ziemann
Xiao-Jun Du
Assam El-Osta
Baker Heart and Diabetes Institute · AUAustralian Regenerative Medicine Institute · AUInstitute of Experimental Cardiology · RUMonash University · AUUniversity of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pharmacological histone deacetylase (HDAC) inhibitors attenuate pathological cardiac remodeling and hypertrophic gene expression; yet, the direct histone targets remain poorly characterized. Since the inhibition of HDAC activity is associated with suppressing hypertrophy, we hypothesized histone acetylation would target genes implicated in cardiac remodeling. Trichostatin A (TSA) regulates cardiac gene expression and attenuates transverse aortic constriction (TAC) induced hypertrophy. We used chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (ChIP-seq) to map, for the first time, genome-wide histone acetylation changes in a preclinical model of pathological cardiac hypertrophy and attenuation of pathogenesis with TSA. Pressure overload-induced cardiac hypertrophy was associated with histone acetylation of genes implicated in cardiac contraction, collagen deposition, inflammation, and extracellular matrix identified by ChIP-seq. Gene set enrichment analysis identified NF-kappa B (NF-κB) transcription factor activation with load induced hypertrophy. Increased histone acetylation was observed on the promoters of NFκB target genes (Icam1, Vcam1, Il21r, Il6ra, Ticam2, Cxcl10) consistent with gene activation in the hypertrophied heart. Surprisingly, TSA attenuated pressure overload-induced cardiac hypertrophy and the suppression of NFκB target genes by broad histone deacetylation. Our results suggest a mechanism for cardioprotection subject to histone deacetylation as a previously unknown target, implicating the importance of inflammation by pharmacological HDAC inhibition. The results of this study provides a framework for HDAC inhibitor function in the heart and argues the long held views of acetylation is subject to more flexibility than previously thought.

Indexed as

AcetylationAnimalsAortaCardiomegalyGene Expression RegulationHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHydroxamic AcidsMaleMice, Inbred C57BLMyocardiumNF-kappa BHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHydroxamic AcidsNF-kappa Btrichostatin AANP, Atrial natriuretic peptideBNP, Brain natriuretic peptideBW, Body Weightcardiac hypertrophycDNA, complementary DNAChIP, Chromatin ImmunoprecipitationchromatinCt, threshold cycle numberCxcl10, Chemokine (C-X-C Motif) ligand 10ENCODE, Encyclopedia of DNA Elements ConsortiumepigeneticsFDR, False Discovery RateFS, Fractional ShorteningGAIIx, Genome Analyzer IIxHDAC, Histone deacetylaseHDAC inhibitorhistone acetylationIcam1, Intercellular adhesion molecule 1Il21r, Interleukin-21 receptorIl6ra, Interleukin-6 receptorLVDd, Left Ventricular Diastolic DimensionLVH, Left Ventricle HypertrophyLV, Left VentricleMACs, Model-based Analysis of ChIP-seqNES, normalized enrichment scorenext generation sequencingNFκB, Nuclear factor of kappa light polypeptide gene enhancer in B-cellsNGS, Next Generation SequencingSEM, Standard Error of the MeanSerca2a, Sarcoplasmic reticulum Ca2+ ATPaseTAC, Transverse Aortic ConstrictionTAC veh, TAC vehicleTF, transcription factorTicam2, Toll-like receptor adaptor molecule 2TL, Tibia LengthTraf3, TNF receptor-associated factor 3TSA, Trichostatin ATSS, Transcription Start SiteUTR, Untranslated regionVcam1, Vascular cell adhesion molecule 1α/βMHC, Alpha/Beta myosin heavy chain

Identifiers

PMID25941940
PMCPMC4622459
OpenAlexW2169881448

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.