Evidence map›Paper›PMID 29302057›Full record

ArticleCell death and differentiation2018

Diabetes induces the activation of pro-ageing miR-34a in the heart, but has differential effects on cardiomyocytes and cardiac progenitor cells.

Ingrid Fomison-Nurse, Eugene Eng Leng Saw, Sophie Gandhi, Pujika Emani Munasinghe, Isabelle Van Hout, Michael J A Williams, Ivor Galvin, Richard Bunton, Philip Davis, Vicky Cameron and 1 more

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

Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
2.9field-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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Five Days Periodic Fasting Elevates Levels of Longevity RelatedInternational journal of molecular sciences · 2021
    Trial
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article
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

11 authors at 2 institutions in 1 country.

Ingrid Fomison-NurseDepartment of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
Eugene Eng Leng SawDepartment of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
Sophie GandhiDepartment of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
Pujika Emani MunasingheDepartment of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
Isabelle Van HoutDepartment of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
Michael J A WilliamsDepartment of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.ORCID http://orcid.org/0000-0003-4822-4962
Ivor GalvinDepartment of Cardiothoracic Surgery, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Richard BuntonDepartment of Cardiothoracic Surgery, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Philip DavisDepartment of Cardiothoracic Surgery, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Vicky CameronChristchurch Heart Institute, University of Otago, Christchurch, New Zealand.
Rajesh KatareDepartment of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand. rajesh.katare@otago.ac.nz.ORCID http://orcid.org/0000-0001-5419-7935
University of Otago · NZNew Zealand Brain Research Institute · NZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Increased apoptosis and premature cellular ageing of the diabetic heart underpin the development of diabetic heart disease. The molecular mechanisms underlying these pathologies are still unclear. Here we determined the role of pro-senescence microRNA (miR)-34a in accelerating the ageing of the diabetic heart. RT-PCR analysis showed a significant increase in the level of circulating miR-34a from early stages in asymptomatic type-2 diabetic individuals compared to non-diabetic controls. We also observed significant upregulation of miR-34a in the type-2 human diabetic heart suggesting circulating miR-34a may be cardiac in origin. Moreover, western blot analysis identified marked downregulation of the pro-survival protein sirtuin 1 (SIRT1), a direct target of miR-34a. Analysis of cultured human adult cardiomyocytes exposed to high glucose and cardiac progenitor cells (CPCs) isolated from the diabetic heart confirmed significant upregulation of miR-34a and downregulation of SIRT1, associated with a marked increase in pro-apoptotic caspase-3/7 activity. Although therapeutic inhibition of miR-34a activity restored SIRT1 expression in both cardiomyocytes and CPCs, p53 expression was further upregulated in cardiomyocytes but conversely downregulated in CPCs. In spite of increased p53, miR-34a inhibition significantly reduced high glucose induced apoptotic cell death in cardiomyocytes. However, this effect was not observed in CPCs, which in fact showed reduced proliferation following miR-34a inhibition. Taken together, our results demonstrate upregulation of miR-34a in the diabetic heart and in the circulation from an early stage of the disease. However, inhibition of miR-34a activity has differential effects depending on the cell type, thereby warranting the need to eliminate off-target effects when introducing miR-based therapy.

Indexed as

Cellular SenescenceAgedAged, 80 and overApoptosisDiabetes Mellitus, Type 2FemaleHumansMaleMicroRNAsMiddle AgedMyocardiumMyocytes, CardiacSirtuin 1Stem CellsMicroRNAsMIRN34 microRNA, humanSIRT1 protein, humanSirtuin 1

Identifiers

PMID29302057
PMCPMC6030067
OpenAlexW2781667286

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.