Evidence map›Paper›PMID 30922078›Full record

ArticleCirculation2019

Inhibition of the Hypoxia-Inducible Factor 1α-Induced Cardiospecific HERNA1 Enhance-Templated RNA Protects From Heart Disease.

Peter Mirtschink, Corinne Bischof, Minh-Duc Pham, Rahul Sharma, Sanjay Khadayate, Geetha Rossi, Niklaus Fankhauser, Shuyang Traub, Samuel Sossalla, Eman Hagag and 8 more

Open access · hybridAbstract read
In one paragraph

Article in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Review
  3. Role of eRNAs in Cardiovascular Diseases.Current cardiology reviews · 2026
    Review
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  7. Article
  8. Hammerhead-type FXR agonists induce an eRNAbioRxiv : the preprint server for biology · 2024
    Article
  9. Article
  10. Review
  11. Dark DNA and stress (Review).International journal of molecular medicine · 2023
    Article
  12. Enhancer RNA (eRNA) in Human Diseases.International journal of molecular sciences · 2022
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  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

18 authors at 8 institutions in 4 countries.

Peter MirtschinkInstitute of Molecular Health Sciences, ETH Zurich, Switzerland (P.M., G.R., N.F., S.T., W.K.).
Corinne BischofMRC Clinical Sciences Centre, Imperial College London, United Kingdom (C.B., S.K., J.K.).
Minh-Duc PhamInstitute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe-University Frankfurt, Germany (C.B., M.-D.P., R.S., P.G., S.D., J.K.).
Rahul SharmaInstitute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe-University Frankfurt, Germany (C.B., M.-D.P., R.S., P.G., S.D., J.K.).
Sanjay KhadayateMRC Clinical Sciences Centre, Imperial College London, United Kingdom (C.B., S.K., J.K.).
Geetha RossiInstitute of Molecular Health Sciences, ETH Zurich, Switzerland (P.M., G.R., N.F., S.T., W.K.).
Niklaus FankhauserInstitute of Molecular Health Sciences, ETH Zurich, Switzerland (P.M., G.R., N.F., S.T., W.K.).
Shuyang TraubInstitute of Molecular Health Sciences, ETH Zurich, Switzerland (P.M., G.R., N.F., S.T., W.K.).
Samuel SossallaDepartment of Internal Medicine III: Cardiology and Angiology, University of Kiel, Germany (S.S.).
Eman HagagInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Dresden, Germany (P.M., E.H.).
Corinne BerthonnecheCardiovascular Assessment Facility, University of Lausanne and CHUV, Switzerland (C.B., A.S.).
Alexandre SarreCardiovascular Assessment Facility, University of Lausanne and CHUV, Switzerland (C.B., A.S.).
Sebastian N StehrDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, and Department of Anesthesiology and Intensive Care Medicine, University Hospital Leipzig, Germany (S.N.S.).
Phillip GroteInstitute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe-University Frankfurt, Germany (C.B., M.-D.P., R.S., P.G., S.D., J.K.).
Thierry PedrazziniDepartment of Medicine, University of Lausanne Medical School, Switzerland (T.P.).
Stefanie DimmelerInstitute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe-University Frankfurt, Germany (C.B., M.-D.P., R.S., P.G., S.D., J.K.).
Wilhelm KrekInstitute of Molecular Health Sciences, ETH Zurich, Switzerland (P.M., G.R., N.F., S.T., W.K.).
Jaya KrishnanMRC Clinical Sciences Centre, Imperial College London, United Kingdom (C.B., S.K., J.K.).
Goethe University Frankfurt · DEETH Zurich · CHUniversity of Lausanne · CHChristian-Albrechts-Universität zu Kiel · DEImperial College London · GBKagawa University Hospital · JPPolyclinic Medical University · CHUniversity Hospital Schleswig-Holstein · DE

Funding

Medical Research Council MC1102/4Medical Research Council MC_UP_1102/4
6 · The paper itself

Abstract

backgroundEnhancers are genomic regulatory elements conferring spatiotemporal and signal-dependent control of gene expression. Recent evidence suggests that enhancers can generate noncoding enhancer RNAs, but their (patho)biological functions remain largely elusive.

methodsWe performed chromatin immunoprecipitation-coupled sequencing of histone marks combined with RNA sequencing of left ventricular biopsies from experimental and genetic mouse models of human cardiac hypertrophy to identify transcripts revealing enhancer localization, conservation with the human genome, and hypoxia-inducible factor 1α dependence. The most promising candidate, hypoxia-inducible enhancer RNA ( HERNA)1, was further examined by investigating its capacity to modulate neighboring coding gene expression by binding to their gene promoters by using chromatin isolation by RNA purification and λN-BoxB tethering-based reporter assays. The role of HERNA1 and its neighboring genes for pathological stress-induced growth and contractile dysfunction, and the therapeutic potential of HERNA1 inhibition was studied in gapmer-mediated loss-of-function studies in vitro using human induced pluripotent stem cell-derived cardiomyocytes and various in vivo models of human pathological cardiac hypertrophy.

resultsHERNA1 is robustly induced on pathological stress. Production of HERNA1 is initiated by direct hypoxia-inducible factor 1α binding to a hypoxia-response element in the histoneH3-lysine27acetylation marks-enriched promoter of the enhancer and confers hypoxia responsiveness to nearby genes including synaptotagmin XVII, a member of the family of membrane-trafficking and Ca

conclusionsHERNA1 is a novel heart-specific noncoding RNA with key regulatory functions in modulating the growth, metabolic, and contractile gene program in disease, and reveals a molecular target amenable to therapeutic exploitation.

Indexed as

AnimalsBinding SitesCardiomyopathy, DilatedCardiomyopathy, HypertrophicCase-Control StudiesDisease Models, AnimalHEK293 CellsHumansHypoxia-Inducible Factor 1, alpha SubunitMaleMice, Inbred C57BLMice, KnockoutMyocytes, CardiacOligonucleotides, AntisensePromoter Regions, GeneticRNA, UntranslatedHIF1A protein, humanHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitOligonucleotides, AntisenseRNA, UntranslatedVHL protein, mouseVon Hippel-Lindau Tumor Suppressor Proteinheart failurehypoxiaRNA

Identifiers

PMID30922078
PMCPMC6571183
OpenAlexW2935248669

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.