Evidence map›Paper›PMID 28455345›Full record

ArticleJournal of the American Heart Association2017

Bilirubin Decreases Macrophage Cholesterol Efflux and ATP-Binding Cassette Transporter A1 Protein Expression.

Dongdong Wang, Anela Tosevska, Elke H Heiß, Angela Ladurner, Christine Mölzer, Marlies Wallner, Andrew Bulmer, Karl-Heinz Wagner, Verena M Dirsch, Atanas G Atanasov

Open access · goldAbstract read
In one paragraph

Article in Journal of the American Heart Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
4.9field-weighted citation impact, top 6% 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

14 citing papers in PubMed, 27 citations in OpenAlex.

  1. Effects of Gilbert syndrome on cardiovascular disease risk reduction: a systematic review.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2026
    Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Bilirubin, a Cardiometabolic Signaling Molecule.Hypertension (Dallas, Tex. : 1979) · 2018
    Review
  11. Article
  12. Observational
  13. Article
  14. Establishment of a Predictive Model for Poor Prognosis of Incomplete Revascularization in Patients with Coronary Heart Disease and Multivessel Disease.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
    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

10 authors at 4 institutions in 5 countries.

Dongdong WangDepartment of Pharmacognosy, University of Vienna, Austria.
Anela TosevskaResearch Platform Active Ageing, University of Vienna, Austria.
Elke H HeißDepartment of Pharmacognosy, University of Vienna, Austria.
Angela LadurnerDepartment of Pharmacognosy, University of Vienna, Austria.
Christine MölzerDepartment of Nutritional Sciences, University of Vienna, Austria.
Marlies WallnerDepartment of Nutritional Sciences, University of Vienna, Austria.
Andrew BulmerSchool of Medical Science and Menzies Health Institute Queensland, Gold Coast, Australia.
Karl-Heinz WagnerResearch Platform Active Ageing, University of Vienna, Austria.
Verena M DirschDepartment of Pharmacognosy, University of Vienna, Austria.
Atanas G AtanasovDepartment of Pharmacognosy, University of Vienna, Austria atanas.atanasov@univie.ac.at.
University of Vienna · ATPolish Academy of Sciences · PLMenzies School of Health Research · AUUniversity of California, Los Angeles · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMild but chronically elevated circulating unconjugated bilirubin is associated with reduced total and low-density lipoprotein cholesterol concentration, which is associated with reduced cardiovascular disease risk. We aimed to investigate whether unconjugated bilirubin influences macrophage cholesterol efflux, as a potential mechanism for the altered circulating lipoprotein concentrations observed in hyperbilirubinemic individuals. METHODS AND

resultsCholesterol efflux from THP-1 macrophages was assessed using plasma obtained from normo- and hyperbilirubinemic (Gilbert syndrome) humans (n=60 per group) or (heterozygote/homozygote Gunn) rats (n=20 per group) as an acceptor. Hyperbilirubinemic plasma from patients with Gilbert syndrome and Gunn rats induced significantly reduced cholesterol efflux compared with normobilirubinemic plasma. Unconjugated bilirubin (3-17.1 μmol/L) exogenously added to plasma- or apolipoprotein A1-supplemented media also decreased macrophage cholesterol efflux in a concentration- and time-dependent manner. We also showed reduced protein expression of the ATP-binding cassette transporter A1 (ABCA1), a transmembrane cholesterol transporter involved in apolipoprotein A1-mediated cholesterol efflux, in THP-1 macrophages treated with unconjugated bilirubin and in peripheral blood mononuclear cells obtained from hyperbilirubinemic individuals. Furthermore, we demonstrated that bilirubin accelerates the degradation rate of the ABCA1 protein in THP-1 macrophages.

conclusionsCholesterol efflux from THP-1 macrophages is decreased in the presence of plasma obtained from humans and rats with mild hyperbilirubinemia. A direct effect of unconjugated bilirubin on cholesterol efflux was demonstrated and is associated with decreased ABCA1 protein expression. These data improve our knowledge concerning bilirubin's impact on cholesterol transport and represent an important advancement in our understanding of bilirubin's role in cardiovascular disease.

Indexed as

AnimalsApolipoprotein A-IATP Binding Cassette Transporter 1BilirubinCase-Control StudiesCholesterolDisease Models, AnimalDown-RegulationFemaleGilbert DiseaseHumansLinear ModelsMacrophagesMaleProteolysisRats, GunnABCA1 protein, humanAPOA1 protein, humanApolipoprotein A-IATP Binding Cassette Transporter 1BilirubinCholesterolATP‐binding cassette transporterbilirubincardiovascular diseasecholesterolcholesterol homeostasis

Identifiers

PMID28455345
PMCPMC5524097
OpenAlexW2607576924

What OpenQuestion 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 OpenQuestion graph.