Evidence map›Paper›PMID 29976768›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2018

Influence of a Coronary Artery Disease-Associated Genetic Variant on FURIN Expression and Effect of Furin on Macrophage Behavior.

Guojun Zhao, Wei Yang, Jingchun Wu, Bairu Chen, Xu Yang, Junhui Chen, David G McVey, Catherine Andreadi, Peng Gong, Tom R Webb and 2 more

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 2 pooled it
1.6field-weighted citation impact, top 16% 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

23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Functional Roles of Furin in Cardio-Cerebrovascular Diseases.ACS pharmacology & translational science · 2024
    Review
  9. Article
  10. Article
  11. TheCirculation research · 2022
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Journal of the American Heart Association · 2020
    Article
  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

12 authors at 5 institutions in 2 countries.

Guojun ZhaoFrom the Shantou University Medical College, China (G.Z., W.Y., J.W., B.C., X.Y., S.Y.).
Wei YangFrom the Shantou University Medical College, China (G.Z., W.Y., J.W., B.C., X.Y., S.Y.).
Jingchun WuFrom the Shantou University Medical College, China (G.Z., W.Y., J.W., B.C., X.Y., S.Y.).
Bairu ChenFrom the Shantou University Medical College, China (G.Z., W.Y., J.W., B.C., X.Y., S.Y.).
Xu YangFrom the Shantou University Medical College, China (G.Z., W.Y., J.W., B.C., X.Y., S.Y.).
Junhui ChenDepartment of Minimally Invasive Intervention, Beijing University Shenzhen Hospital, China (J.C.).
David G McVeyDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, United Kingdom (D.G.M., C.A., P.G., T.R.W., N.J.S., S.Y.).
Catherine AndreadiDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, United Kingdom (D.G.M., C.A., P.G., T.R.W., N.J.S., S.Y.).
Peng GongDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, United Kingdom (D.G.M., C.A., P.G., T.R.W., N.J.S., S.Y.).
Tom R WebbDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, United Kingdom (D.G.M., C.A., P.G., T.R.W., N.J.S., S.Y.).
Nilesh J SamaniFrom the Shantou University Medical College, China (G.Z., W.Y., J.W., B.C., X.Y., S.Y.).
Shu YeDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, United Kingdom (D.G.M., C.A., P.G., T.R.W., N.J.S., S.Y.).
Shantou University · CNBeijing Chuiyangliu Hospital · CNGuilin Medical University · CNShantou University Medical College · CNUniversity of Leicester · GB

Funding

British Heart Foundation PG/16/9/31995British Heart Foundation RG/16/13/32609British Heart Foundation SP/16/4/32697
6 · The paper itself

Abstract

Objective- Genome-wide association studies have revealed a robust association between genetic variation on chromosome 15q26.1 and coronary artery disease (CAD) susceptibility; however, the underlying biological mechanism is still unknown. The lead CAD-associated genetic variant (rs17514846) at this locus resides in the FURIN gene. In advanced atherosclerotic plaques, furin is expressed primarily in macrophages. We investigated whether this CAD-associated variant alters FURIN expression and whether furin affects monocyte/macrophage behavior. Approach and Results- A quantitative reverse transcription polymerase chain reaction analysis showed that leukocytes from individuals carrying the CAD risk allele (A) of rs17514846 had increased FURIN expression. A chromatin immunoprecipitation assay revealed higher RNA polymerase II occupancy in the FURIN gene in mononuclear cells of individuals carrying this allele. A reporter gene assay in transiently transfected monocytes/macrophages indicated that the CAD risk allele had higher transcriptional activity than the nonrisk allele (C). An analysis of isogenic monocyte cell lines created by CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing showed that isogenic cells with the A/A genotype for rs17514846 had higher FURIN expression levels than the isogenic cells with the C/C genotype. An electrophoretic mobility shift assay exhibited preferential binding of a nuclear protein to the risk allele. Studies of monocytes/macrophages with lentivirus-mediated furin overexpression or shRNA (short hairpin RNA)-induced furin knockdown showed that furin overexpression promoted monocyte/macrophage migration, increased proliferation, and reduced apoptosis whereas furin knockdown had the opposite effects. Conclusions- Our study shows that the CAD-associated genetic variant increases FURIN expression and that furin promotes monocyte/macrophage migration and proliferation while inhibiting apoptosis, providing a biological mechanism for the association between variation at the chromosome 15q26.1 locus and CAD risk.

Indexed as

Macrophage ActivationPolymorphism, Single NucleotideAnimalsApoptosisCase-Control StudiesCell MovementCell ProliferationCoronary Artery DiseaseFurinGenetic Predisposition to DiseaseHeterozygoteHomozygoteHumansMacrophagesMicePhenotypeFurinFURIN protein, humanFurin protein, mousecoronary artery diseasefurinmacrophagesmonocytespolymorphism, single nucleotide

Identifiers

PMID29976768
PMCPMC6092112
OpenAlexW2861291694

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.