Evidence map›Paper›PMID 23658787›Full record

ArticlePloS one2013

Nicotinic acid receptor GPR109A is down-regulated in human macrophage-derived foam cells.

Joshua T Chai, Janet E Digby, Neil Ruparelia, Andrew Jefferson, Ashok Handa, Robin P Choudhury

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
3.2field-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

10 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. 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

6 authors at 1 institution in 1 country.

Joshua T ChaiDivision of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom.
Janet E Digby
Neil Ruparelia
Andrew Jefferson
Ashok Handa
Robin P Choudhury
University of Oxford · GB

Funding

British Heart FoundationMedical Research Council MR/K00266X/1Wellcome Trust 088291Wellcome Trust 090532
6 · The paper itself

Abstract

Nicotinic acid (NA) regresses atherosclerosis in human imaging studies and reduces atherosclerosis in mice, mediated by myeloid cells, independent of lipoproteins. Since GPR109A is expressed by human monocytes, we hypothesized that NA may drive cholesterol efflux from foam cells. In THP-1 cells NA suppressed LPS-induced mRNA transcription of MCP-1 by 76.6±12.2% (P<0.01) and TNFα by 56.1±11.5% (P<0.01), yet restored LPS-induced suppression of PPARγ transcription by 536.5±46.4% (P<0.001) and its downstream effector CD36 by 116.8±19.8% (P<0.01). Whilst direct PPARγ-agonism promoted cholesterol efflux from THP-1 derived foam cells by 37.7±3.1% (P<0.01) and stimulated transcription of LXRα by 87.9±9.5% (P<0.001) and ABCG1 by 101.2±15.5% (P<0.01), NA showed no effect in foam cells on either cholesterol efflux or key RCT genes transcription. Upon foam cell induction, NA lost its effect on PPARγ and cAMP pathways, since its receptor, GPR109A, was down-regulated by foam cell transformation. This observation was confirmed in explanted human carotid plaques. In conclusion, despite NA's anti-inflammatory effect on human macrophages, it has no effect on foam cells in reverse cholesterol transport; due to GPR109A down-regulation.

Indexed as

Down-RegulationATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 1BenzophenonesBiological TransportCell LineCholesterolCyclic AMPFoam CellsHumansInflammation MediatorsLipopolysaccharidesNiacinOrphan Nuclear ReceptorsPlaque, AtheroscleroticABCG1 protein, humanATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 1BenzophenonesCholesterolCyclic AMPGW 1929HCAR2 protein, humanInflammation MediatorsLipopolysaccharidesNiacinOrphan Nuclear ReceptorsPPAR gammaReceptors, G-Protein-CoupledReceptors, NicotinicTyrosine

Identifiers

PMID23658787
PMCPMC3642175
OpenAlexW1967111806

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.