Evidence map›Paper›PMID 29161413›Full record

ArticleNucleic acids research2018

NRF2 regulates endothelial glycolysis and proliferation with miR-93 and mediates the effects of oxidized phospholipids on endothelial activation.

Suvi M Kuosmanen, Emilia Kansanen, Minna U Kaikkonen, Virve Sihvola, Kati Pulkkinen, Henna-Kaisa Jyrkkänen, Pauli Tuoresmäki, Juha Hartikainen, Mikko Hippeläinen, Hannu Kokki and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% 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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Metabolic Responses to Redox Stress in Vascular Cells.Antioxidants & redox signaling · 2024
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Pathogenic role of PFKFB3 in endothelial inflammatory diseases.Frontiers in molecular biosciences · 2024
    Review
  13. Article
  14. Article
  15. Endothelial mechanobiology in atherosclerosis.Cardiovascular research · 2023
    Review
  16. Review
  17. Article
  18. Review
  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

13 authors at 2 institutions in 1 country.

Suvi M KuosmanenA.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.
Minna U KaikkonenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Virve SihvolaA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Kati PulkkinenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Henna-Kaisa JyrkkänenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Pauli TuoresmäkiInstitute of Biomedicine, School of Medicine, University of Eastern Finland, 70211 Kuopio, Finland.
Juha HartikainenSchool of Medicine, University of Eastern Finland, 70211 Kuopio, Finland.
Mikko HippeläinenHeart Centre, 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.
Sami HeikkinenInstitute of Biomedicine, School of Medicine, University of Eastern Finland, 70211 Kuopio, Finland.
Anna-Liisa LevonenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
University of Eastern Finland · FIKuopio University Hospital · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Phospholipids, such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC), are the major components of cell membranes. Their exposure to reactive oxygen species creates oxidized phospholipids, which predispose to the development of chronic inflammatory diseases and metabolic disorders through endothelial activation and dysfunction. Although the effects of oxidized PAPC (oxPAPC) on endothelial cells have been previously studied, the underlying molecular mechanisms evoking biological responses remain largely unknown. Here, we investigated the molecular mechanisms of oxPAPC function with a special emphasis on NRF2-regulated microRNAs (miRNAs) in human umbilical vein endothelial cells (HUVECs) utilizing miRNA profiling, global run-on sequencing (GRO-seq), genome-wide NRF2 binding model, and RNA sequencing (RNA-seq) with miRNA overexpression and silencing. We report that the central regulators of endothelial activity, KLF2 for quiescence, PFKFB3 for glycolysis, and VEGFA, FOXO1 and MYC for growth and proliferation, are regulated by transcription factor NRF2 and the NRF2-regulated miR-106b∼25 cluster member, miR-93, in HUVECs. Mechanistically, oxPAPC was found to induce glycolysis and proliferation NRF2-dependently, and oxPAPC-dependent induction of the miR-106b∼25 cluster was mediated by NRF2. Additionally, several regulatory loops were established between NRF2, miR-93 and the essential regulators of healthy endothelium, collectively implying that NRF2 controls the switch between the quiescent and the proliferative endothelial states together with miR-93.

Indexed as

AntagomirsCell ProliferationForkhead Box Protein O1Gene Expression ProfilingGene Expression RegulationGlycolysisHumansHuman Umbilical Vein Endothelial CellsKruppel-Like Transcription FactorsMicroRNAsNF-E2-Related Factor 2Oxidation-ReductionPhosphatidylcholinesPhosphofructokinase-2Primary Cell CultureProto-Oncogene Proteins c-myc1-palmitoyl-2-arachidonyl-3-phosphorylcholineAntagomirsForkhead Box Protein O1FOXO1 protein, humanKLF2 protein, humanKruppel-Like Transcription FactorsMicroRNAsMIRN93 microRNA, humanMYC protein, humanNFE2L2 protein, humanNF-E2-Related Factor 2oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholinePFKFB3 protein, humanPhosphatidylcholinesPhosphofructokinase-2Proto-Oncogene Proteins c-mycReactive Oxygen SpeciesVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID29161413
PMCPMC5815049
OpenAlexW2768653170

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.