Evidence map›Paper›PMID 26371176›Full record

ArticleCirculation. Heart failure2015

HDACs Regulate miR-133a Expression in Pressure Overload-Induced Cardiac Fibrosis.

Ludivine Renaud, Lillianne G Harris, Santhosh K Mani, Harinath Kasiganesan, James C Chou, Catalin F Baicu, An Van Laer, Adam W Akerman, Robert E Stroud, Jeffrey A Jones and 2 more

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

Article in Circulation. Heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

39 citing papers in PubMed, 68 citations in OpenAlex.

  1. Review
  2. Review
  3. Epigenetic Mechanisms in Heart Diseases.Reviews in cardiovascular medicine · 2025
    Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Epigenetics and environmental health.Frontiers of medicine · 2024
    Review
  9. Article
  10. Review
  11. Review
  12. Epigenetics as a versatile regulator of fibrosis.Journal of translational medicine · 2023
    Review
  13. Review
  14. Review
  15. Non-coding RNAs: Important participants in cardiac fibrosis.Frontiers in cardiovascular medicine · 2022
    Review
  16. Review
  17. Review
  18. Article
  19. Review
  20. Review
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

12 authors at 1 institution in 1 country.

Ludivine RenaudFrom the Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute (L.R., L.G.H., S.K.M., H.K., C.F.B., A.V.L., M.R.Z., D.R.M.), Division of Cardiothoracic Surgery, Department of Cardiothoracic Surgical Research (A.W.A., R.E.S., J.A.J.), and Department of Drug Discovery and Biomedical Sciences, College of Pharmacy (J.C.C.), The Medical University of South Carolina, Charleston; and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J., M.R.Z., D.R.M.).
Lillianne G HarrisFrom the Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute (L.R., L.G.H., S.K.M., H.K., C.F.B., A.V.L., M.R.Z., D.R.M.), Division of Cardiothoracic Surgery, Department of Cardiothoracic Surgical Research (A.W.A., R.E.S., J.A.J.), and Department of Drug Discovery and Biomedical Sciences, College of Pharmacy (J.C.C.), The Medical University of South Carolina, Charleston; and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J., M.R.Z., D.R.M.).
Santhosh K ManiFrom the Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute (L.R., L.G.H., S.K.M., H.K., C.F.B., A.V.L., M.R.Z., D.R.M.), Division of Cardiothoracic Surgery, Department of Cardiothoracic Surgical Research (A.W.A., R.E.S., J.A.J.), and Department of Drug Discovery and Biomedical Sciences, College of Pharmacy (J.C.C.), The Medical University of South Carolina, Charleston; and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J., M.R.Z., D.R.M.).
Harinath KasiganesanFrom the Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute (L.R., L.G.H., S.K.M., H.K., C.F.B., A.V.L., M.R.Z., D.R.M.), Division of Cardiothoracic Surgery, Department of Cardiothoracic Surgical Research (A.W.A., R.E.S., J.A.J.), and Department of Drug Discovery and Biomedical Sciences, College of Pharmacy (J.C.C.), The Medical University of South Carolina, Charleston; and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J., M.R.Z., D.R.M.).
James C ChouFrom the Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute (L.R., L.G.H., S.K.M., H.K., C.F.B., A.V.L., M.R.Z., D.R.M.), Division of Cardiothoracic Surgery, Department of Cardiothoracic Surgical Research (A.W.A., R.E.S., J.A.J.), and Department of Drug Discovery and Biomedical Sciences, College of Pharmacy (J.C.C.), The Medical University of South Carolina, Charleston; and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J., M.R.Z., D.R.M.).
Catalin F BaicuFrom the Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute (L.R., L.G.H., S.K.M., H.K., C.F.B., A.V.L., M.R.Z., D.R.M.), Division of Cardiothoracic Surgery, Department of Cardiothoracic Surgical Research (A.W.A., R.E.S., J.A.J.), and Department of Drug Discovery and Biomedical Sciences, College of Pharmacy (J.C.C.), The Medical University of South Carolina, Charleston; and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J., M.R.Z., D.R.M.).
An Van LaerFrom the Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute (L.R., L.G.H., S.K.M., H.K., C.F.B., A.V.L., M.R.Z., D.R.M.), Division of Cardiothoracic Surgery, Department of Cardiothoracic Surgical Research (A.W.A., R.E.S., J.A.J.), and Department of Drug Discovery and Biomedical Sciences, College of Pharmacy (J.C.C.), The Medical University of South Carolina, Charleston; and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J., M.R.Z., D.R.M.).
Adam W AkermanFrom the Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute (L.R., L.G.H., S.K.M., H.K., C.F.B., A.V.L., M.R.Z., D.R.M.), Division of Cardiothoracic Surgery, Department of Cardiothoracic Surgical Research (A.W.A., R.E.S., J.A.J.), and Department of Drug Discovery and Biomedical Sciences, College of Pharmacy (J.C.C.), The Medical University of South Carolina, Charleston; and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J., M.R.Z., D.R.M.).
Robert E StroudFrom the Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute (L.R., L.G.H., S.K.M., H.K., C.F.B., A.V.L., M.R.Z., D.R.M.), Division of Cardiothoracic Surgery, Department of Cardiothoracic Surgical Research (A.W.A., R.E.S., J.A.J.), and Department of Drug Discovery and Biomedical Sciences, College of Pharmacy (J.C.C.), The Medical University of South Carolina, Charleston; and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J., M.R.Z., D.R.M.).
Jeffrey A JonesFrom the Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute (L.R., L.G.H., S.K.M., H.K., C.F.B., A.V.L., M.R.Z., D.R.M.), Division of Cardiothoracic Surgery, Department of Cardiothoracic Surgical Research (A.W.A., R.E.S., J.A.J.), and Department of Drug Discovery and Biomedical Sciences, College of Pharmacy (J.C.C.), The Medical University of South Carolina, Charleston; and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J., M.R.Z., D.R.M.).
Michael R ZileFrom the Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute (L.R., L.G.H., S.K.M., H.K., C.F.B., A.V.L., M.R.Z., D.R.M.), Division of Cardiothoracic Surgery, Department of Cardiothoracic Surgical Research (A.W.A., R.E.S., J.A.J.), and Department of Drug Discovery and Biomedical Sciences, College of Pharmacy (J.C.C.), The Medical University of South Carolina, Charleston; and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J., M.R.Z., D.R.M.).
Donald R MenickFrom the Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute (L.R., L.G.H., S.K.M., H.K., C.F.B., A.V.L., M.R.Z., D.R.M.), Division of Cardiothoracic Surgery, Department of Cardiothoracic Surgical Research (A.W.A., R.E.S., J.A.J.), and Department of Drug Discovery and Biomedical Sciences, College of Pharmacy (J.C.C.), The Medical University of South Carolina, Charleston; and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J., M.R.Z., D.R.M.). menickd@musc.edu.
University of Utah · US

Funding

TRAINING TO IMPROVE CARDIOVASCULAR THERAPIEST32HL007260 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MENICK, DONALD R. · 1985 to 2021
$11.1M
South Carolina Clinical & Translational Research Institute (SCTR)UL1TR000062 · NCATS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BRADY, KATHLEEN T. · 2012 to 2014
$9.4M
Transmembrane Proteolytic Induction and Thoracic AneurysmsR01HL102121 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI IKONOMIDIS, JOHN S · 2011 to 2019
$3.0M
Extracellular Matrix in Hypertensive Heart Disease & Transition to Heart FailureR01HL123478 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ZILE, MICHAEL R · 2015 to 2018
$1.5M
MAP4 REGULATION OF CARDIAC MICROTUBULE NETWORK DENSITYR01HL094545 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MENICK, DONALD R. · 2010 to 2013
$1.5M
Role of Protein Acetylation in Ncx1 ExpressionR01HL095696 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MENICK, DONALD R. · 2009 to 2012
$1.5M
Extracellular Matrix in Hypertensive Heart Disease & Transition to Heart FailureR56HL123478 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ZILE, MICHAEL R · 2014 to 2014
$387k
Connexin Distribution in Physiological Versus Pathological Cardiac HypertrophyI01BX000487 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI ZILE, MICHAEL R · 2009 to 2013
–
AGE/RAGE Interaction in Patients with Pressure Overload-Induced Heart FailureI01CX000415 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI ZILE, MICHAEL R · 2011 to 2014
–
Regulatroy Role of HDAC in Post-MI Ventricular RemodelingI01BX002327 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI MENICK, DONALD R. · 2015 to 2023
–
Transforming Growth Factor-beta Signaling Pathways in Thoracic Aortic AneurysmsI01BX000904 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI JONES, JEFFREY A. · 2011 to 2023
–
BLRD VA I01 BX000487BLRD VA I01 BX000904BLRD VA I01 BX002327CSRD VA I01 CX000415NCATS NIH HHS UL1 TR000062NCATS NIH HHS UL1TR000062NHLBI NIH HHS R01 HL094545NHLBI NIH HHS R01HL094545NHLBI NIH HHS R01 HL095696NHLBI NIH HHS R01 HL102121NHLBI NIH HHS R01 HL123478NHLBI NIH HHS R01HL123478NHLBI NIH HHS R56 HL123478NHLBI NIH HHS R56HL123478NHLBI NIH HHS T32 HL007260NHLBI NIH HHS T32HL07260
6 · The paper itself

Abstract

backgroundMicroRNAs (miRNAs) and histone deacetylases (HDACs) serve a significant role in the pathogenesis of a variety of cardiovascular diseases. The transcriptional regulation of miRNAs is poorly understood in cardiac hypertrophy. We investigated whether the expression of miR-133a is epigenetically regulated by class I and IIb HDACs during hypertrophic remodeling. METHODS AND

resultsTransverse aortic constriction (TAC) was performed in CD1 mice to induce pressure overload hypertrophy. Mice were treated with class I and IIb HDAC inhibitor (HDACi) via drinking water for 2 and 4 weeks post TAC. miRNA expression was determined by real-time polymerase chain reaction. Echocardiography was performed at baseline and post TAC end points for structural and functional assessment. Chromatin immunoprecipitation was used to identify HDACs and transcription factors associated with miR-133a promoter. miR-133a expression was downregulated by 0.7- and 0.5-fold at 2 and 4 weeks post TAC, respectively, when compared with vehicle control (P<0.05). HDAC inhibition prevented this significant decrease 2 weeks post TAC and maintained miR-133a expression near vehicle control levels, which coincided with (1) a decrease in connective tissue growth factor expression, (2) a reduction in cardiac fibrosis and left atrium diameter (marker of end-diastolic pressure), suggesting an improvement in diastolic function. Chromatin immunoprecipitation analysis revealed that HDAC1 and HDAC2 are present on the miR-133a enhancer regions.

conclusionsThe results reveal that HDACs play a role in the regulation of pressure overload-induced miR-133a downregulation. This work is the first to provide insight into an epigenetic-miRNA regulatory pathway in pressure overload-induced cardiac fibrosis.

Indexed as

AnimalsCardiomegalyCell Culture TechniquesDisease Models, AnimalFibroblastsHistone Deacetylase InhibitorsHistone DeacetylasesHumansHydroxamic AcidsMiceMicroRNAsVorinostatHistone Deacetylase InhibitorsHistone DeacetylasesHydroxamic AcidsMicroRNAsMIRN133 microRNA, humanMirn133 microRNA, mouseVorinostatepigenomicsheart ventricleshistone deacetylasehypertrophymicroRNA

Identifiers

PMID26371176
PMCPMC4651803
OpenAlexW2180607116

What OpenQuestion holds

Textmetadata
LicenceTDM
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.