Evidence map›Paper›PMID 26838786›Full record

ArticleCirculation research2016

DNA Methylation Indicates Susceptibility to Isoproterenol-Induced Cardiac Pathology and Is Associated With Chromatin States.

Haodong Chen, Luz D Orozco, Jessica Wang, Christoph D Rau, Liudmilla Rubbi, Shuxun Ren, Yibin Wang, Matteo Pellegrini, Aldons J Lusis, Thomas M Vondriska

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

Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

33 citing papers in PubMed, 48 citations in OpenAlex.

  1. Review
  2. Nuclear Proteome Map of Mouse Heart Chambers.Molecular & cellular proteomics : MCP · 2026
    Article
  3. Cardiac epigenome in heart development and disease.Nature reviews. Cardiology · 2026
    Review
  4. Systematic analysis ofTranslational andrology and urology · 2026
    Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Clinical epigenomics for cardiovascular disease: Diagnostics and therapies.Journal of molecular and cellular cardiology · 2021
    Review
  19. Review
  20. Epigenetics and Heart Failure.International journal of molecular sciences · 2020
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Haodong ChenFrom the Departments of Anesthesiology and Perioperative Medicine (H.C., C.D.R., S.R., Y.W., T.M.V.), Human Genetics (A.J.L.), Microbiology, Immunology and Molecular Genetics (A.J.L.), Molecular, Cellular and Development Biology (L.D.O., L.R., M.P.), Medicine/Cardiology (J.W., Y.W., A.J.L., T.M.V.), and Physiology, David Geffen School of Medicine, University of California, Los Angeles (Y.W., T.M.V.). hdchen.ucla@gmail.com tvondriska@mednet.ucla.edu.
Luz D OrozcoFrom the Departments of Anesthesiology and Perioperative Medicine (H.C., C.D.R., S.R., Y.W., T.M.V.), Human Genetics (A.J.L.), Microbiology, Immunology and Molecular Genetics (A.J.L.), Molecular, Cellular and Development Biology (L.D.O., L.R., M.P.), Medicine/Cardiology (J.W., Y.W., A.J.L., T.M.V.), and Physiology, David Geffen School of Medicine, University of California, Los Angeles (Y.W., T.M.V.).
Jessica WangFrom the Departments of Anesthesiology and Perioperative Medicine (H.C., C.D.R., S.R., Y.W., T.M.V.), Human Genetics (A.J.L.), Microbiology, Immunology and Molecular Genetics (A.J.L.), Molecular, Cellular and Development Biology (L.D.O., L.R., M.P.), Medicine/Cardiology (J.W., Y.W., A.J.L., T.M.V.), and Physiology, David Geffen School of Medicine, University of California, Los Angeles (Y.W., T.M.V.).
Christoph D RauFrom the Departments of Anesthesiology and Perioperative Medicine (H.C., C.D.R., S.R., Y.W., T.M.V.), Human Genetics (A.J.L.), Microbiology, Immunology and Molecular Genetics (A.J.L.), Molecular, Cellular and Development Biology (L.D.O., L.R., M.P.), Medicine/Cardiology (J.W., Y.W., A.J.L., T.M.V.), and Physiology, David Geffen School of Medicine, University of California, Los Angeles (Y.W., T.M.V.).
Liudmilla RubbiFrom the Departments of Anesthesiology and Perioperative Medicine (H.C., C.D.R., S.R., Y.W., T.M.V.), Human Genetics (A.J.L.), Microbiology, Immunology and Molecular Genetics (A.J.L.), Molecular, Cellular and Development Biology (L.D.O., L.R., M.P.), Medicine/Cardiology (J.W., Y.W., A.J.L., T.M.V.), and Physiology, David Geffen School of Medicine, University of California, Los Angeles (Y.W., T.M.V.).
Shuxun RenFrom the Departments of Anesthesiology and Perioperative Medicine (H.C., C.D.R., S.R., Y.W., T.M.V.), Human Genetics (A.J.L.), Microbiology, Immunology and Molecular Genetics (A.J.L.), Molecular, Cellular and Development Biology (L.D.O., L.R., M.P.), Medicine/Cardiology (J.W., Y.W., A.J.L., T.M.V.), and Physiology, David Geffen School of Medicine, University of California, Los Angeles (Y.W., T.M.V.).
Yibin WangFrom the Departments of Anesthesiology and Perioperative Medicine (H.C., C.D.R., S.R., Y.W., T.M.V.), Human Genetics (A.J.L.), Microbiology, Immunology and Molecular Genetics (A.J.L.), Molecular, Cellular and Development Biology (L.D.O., L.R., M.P.), Medicine/Cardiology (J.W., Y.W., A.J.L., T.M.V.), and Physiology, David Geffen School of Medicine, University of California, Los Angeles (Y.W., T.M.V.).
Matteo PellegriniFrom the Departments of Anesthesiology and Perioperative Medicine (H.C., C.D.R., S.R., Y.W., T.M.V.), Human Genetics (A.J.L.), Microbiology, Immunology and Molecular Genetics (A.J.L.), Molecular, Cellular and Development Biology (L.D.O., L.R., M.P.), Medicine/Cardiology (J.W., Y.W., A.J.L., T.M.V.), and Physiology, David Geffen School of Medicine, University of California, Los Angeles (Y.W., T.M.V.).
Aldons J LusisFrom the Departments of Anesthesiology and Perioperative Medicine (H.C., C.D.R., S.R., Y.W., T.M.V.), Human Genetics (A.J.L.), Microbiology, Immunology and Molecular Genetics (A.J.L.), Molecular, Cellular and Development Biology (L.D.O., L.R., M.P.), Medicine/Cardiology (J.W., Y.W., A.J.L., T.M.V.), and Physiology, David Geffen School of Medicine, University of California, Los Angeles (Y.W., T.M.V.).
Thomas M VondriskaFrom the Departments of Anesthesiology and Perioperative Medicine (H.C., C.D.R., S.R., Y.W., T.M.V.), Human Genetics (A.J.L.), Microbiology, Immunology and Molecular Genetics (A.J.L.), Molecular, Cellular and Development Biology (L.D.O., L.R., M.P.), Medicine/Cardiology (J.W., Y.W., A.J.L., T.M.V.), and Physiology, David Geffen School of Medicine, University of California, Los Angeles (Y.W., T.M.V.). hdchen.ucla@gmail.com tvondriska@mednet.ucla.edu.
Laboratory of Molecular Genetics · PL

Funding

Training Grant in Genomic Analysis and InterpretationT32HG002536 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Valerie A Arboleda, Harold Pimentel · 2002 to 2026
$8.6M
Dynamics of Cardiac Nuclei in Heart DiseaseR01HL105699 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VONDRISKA, THOMAS M. · 2011 to 2025
$5.0M
Systems Approach to Unraveling the Genetic Basis of Heart FailureR01HL114437 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DENG, MARIO C., KARMA, ALAIN S · 2013 to 2016
$4.7M
Epigenomic Mechanisms of Heart FailureR01HL129639 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VONDRISKA, THOMAS M. · 2015 to 2018
$2.6M
Systems Analysis of Cardiac Chromatin StructureR01HL115238 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VONDRISKA, THOMAS M. · 2012 to 2016
$1.9M
NHGRI NIH HHS T32 HG002536NHLBI NIH HHS HL-105699NHLBI NIH HHS HL-115238NHLBI NIH HHS R01 HL105699NHLBI NIH HHS R01 HL114437NHLBI NIH HHS R01 HL115238NHLBI NIH HHS R01 HL129639
6 · The paper itself

Abstract

rationaleOnly a small portion of the known heritability of cardiovascular diseases, such as heart failure, can be explained based on single-gene mutations. Chromatin structure and regulation provide a substrate through which genetic differences in noncoding regions may affect cellular function and response to disease, but the mechanisms are unknown.

objectiveWe conducted genome-wide measurements of DNA methylation in different strains of mice that are susceptible and resistant to isoproterenol-induced dysfunction to test the hypothesis that this epigenetic mark may play a causal role in the development of heart failure. METHODS AND

resultsBALB/cJ and BUB/BnJ mice, determined to be susceptible and resistant to isoproterenol-induced heart failure, respectively, were administered the drug for 3 weeks via osmotic minipump. Reduced representational bisulfite sequencing was then used to compare the differences between the cardiac DNA methylomes in the basal state between strains and then after isoproterenol treatment. Single-base resolution DNA methylation measurements were obtained and revealed a bimodal distribution of methylation in the heart, enriched in lone intergenic CpGs and depleted from CpG islands around genes. Isoproterenol induced global decreases in methylation in both strains; however, the basal methylation pattern between strains shows striking differences that may be predictive of disease progression before environmental stress. The global correlation between promoter methylation and gene expression (as measured by microarray) was modest and revealed itself only with focused analyses of transcription start site and gene body regions (in contrast to when gene methylation was examined in toto). Modules of comethylated genes displayed correlation with other protein-based epigenetic marks, supporting the hypothesis that chromatin modifications act in a combinatorial manner to specify transcriptional phenotypes in the heart.

conclusionsThis study provides the first single-base resolution map of the mammalian cardiac DNA methylome and the first case-control analysis of the changes in DNA methylation with heart failure. The findings demonstrate marked genetic differences in DNA methylation that are associated with disease progression.

Indexed as

AnimalsCardiotonic AgentsChromatinCpG IslandsDisease SusceptibilityDNA MethylationFemaleHeart FailureIsoproterenolMiceMice, Inbred BALB CSpecies SpecificityCardiotonic AgentsChromatinIsoproterenolchromatinDNA methylationepigenomicsgeneticsheart failure

Identifiers

PMID26838786
PMCPMC4779427
OpenAlexW2239798180

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Registered trials

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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.