Evidence map›Paper›PMID 32683448›Full record

ArticleCardiovascular research2021

NRF2 is a key regulator of endothelial microRNA expression under proatherogenic stimuli.

Suvi Linna-Kuosmanen, Vanesa Tomas Bosch, Pierre R Moreau, Maria Bouvy-Liivrand, Henri Niskanen, Emilia Kansanen, Annukka Kivelä, Juha Hartikainen, Mikko Hippeläinen, Hannu Kokki and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

37 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Connecting the Dots: How MicroRNAs Link Asthma and Atherosclerosis.International journal of molecular sciences · 2025
    Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Exosome is a Fancy Mobile Sower of Ferroptosis.Journal of cardiovascular translational research · 2024
    Review
  16. Review
  17. Transcriptomic analysis reveals molecular characterization and immune landscape of PANoptosis-related genes in atherosclerosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024
    Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 3 countries.

Suvi Linna-KuosmanenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Vanesa Tomas BoschA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Pierre R MoreauA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Maria Bouvy-LiivrandSchool of Medicine, University of Eastern Finland, 70211 Kuopio, Finland.
Henri NiskanenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Emilia KansanenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Annukka KiveläA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Juha HartikainenSchool of Medicine, University of Eastern Finland, 70211 Kuopio, Finland.
Mikko HippeläinenHeart Center, Kuopio University Hospital, 70211 Kuopio, Finland.
Hannu KokkiSchool of Medicine, University of Eastern Finland, 70211 Kuopio, Finland.
Pasi TaviA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Anna-Liisa LevonenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Minna U KaikkonenA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
University of Eastern Finland · FIKuopio University Hospital · FITallinn University of Technology · EE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsOxidized phospholipids and microRNAs (miRNAs) are increasingly recognized to play a role in endothelial dysfunction driving atherosclerosis. NRF2 transcription factor is one of the key mediators of the effects of oxidized phospholipids, but the gene regulatory mechanisms underlying the process remain obscure. Here, we investigated the genome-wide effects of oxidized phospholipids on transcriptional gene regulation in human umbilical vein endothelial cells and aortic endothelial cells with a special focus on miRNAs. METHODS AND

resultsWe integrated data from HiC, ChIP-seq, ATAC-seq, GRO-seq, miRNA-seq, and RNA-seq to provide deeper understanding of the transcriptional mechanisms driven by NRF2 in response to oxidized phospholipids. We demonstrate that presence of NRF2 motif and its binding is more prominent in the vicinity of up-regulated transcripts and transcriptional initiation represents the most likely mechanism of action. We further identified NRF2 as a novel regulator of over 100 endothelial pri-miRNAs. Among these, we characterize two hub miRNAs miR-21-5p and miR-100-5p and demonstrate their opposing roles on mTOR, VEGFA, HIF1A, and MYC expressions. Finally, we provide evidence that the levels of miR-21-5p and miR-100-5p in exosomes are increased upon senescence and exhibit a trend to correlate with the severity of coronary artery disease.

conclusionAltogether, our analysis provides an integrative view into the regulation of transcription and miRNA function that could mediate the proatherogenic effects of oxidized phospholipids in endothelial cells.

Indexed as

TranscriptomeAtherosclerosisCells, CulturedCellular SenescenceDatabases, GeneticGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksHumansHuman Umbilical Vein Endothelial CellsMicroRNAsNF-E2-Related Factor 2Oxidation-ReductionPhosphatidylcholinesPlaque, Atherosclerotic1-palmitoyl-2-arachidonyl-3-phosphorylcholineMicroRNAsMIRN100 microRNA, humanMIRN126 microRNA, humanMIRN21 microRNA, humanNFE2L2 protein, humanNF-E2-Related Factor 2PhosphatidylcholinesmiR-21-5p • miR-100-5p •  NRF2 • Atherosclerosis

Identifiers

PMID32683448
PMCPMC8064437
OpenAlexW3043576981

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.