Evidence map›Paper›PMID 29588315›Full record

ArticleCirculation2018

Cholesterol Efflux Pathways Suppress Inflammasome Activation, NETosis, and Atherogenesis.

Marit Westerterp, Panagiotis Fotakis, Mireille Ouimet, Andrea E Bochem, Hanrui Zhang, Matthew M Molusky, Wei Wang, Sandra Abramowicz, Sacha la Bastide-van Gemert, Nan Wang and 5 more

Open access · greenAbstract read
In one paragraph

Article in Circulation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers.

0numbers the graph read from it
0cells of the map it votes in
210citing papers in PubMed
10.9field-weighted citation impact, top 1% 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

210 citing papers in PubMed, 312 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Interleukin-18 Inhibition Aggravates Atherosclerosis in Jak2JACC. Basic to translational science · 2026
    Article
  8. Article
  9. Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026
    Review
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  15. Article
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150 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 4 countries.

Marit WesterterpDivision of Molecular Medicine (M.W., P.F., A.E.B., M.M.M., W.W., S.A., N.W., C.L.W., A.R.T.).
Panagiotis FotakisDivision of Molecular Medicine (M.W., P.F., A.E.B., M.M.M., W.W., S.A., N.W., C.L.W., A.R.T.).
Mireille OuimetDepartment of Medicine, Division of Cardiology, New York University Medical Center, NY (M.O., K.J.M.).
Andrea E BochemDivision of Molecular Medicine (M.W., P.F., A.E.B., M.M.M., W.W., S.A., N.W., C.L.W., A.R.T.).
Hanrui ZhangDivision of Cardiology (H.Z., M.P.R.), Department of Medicine, Columbia University, New York, NY.
Matthew M MoluskyDivision of Molecular Medicine (M.W., P.F., A.E.B., M.M.M., W.W., S.A., N.W., C.L.W., A.R.T.).
Wei WangDivision of Molecular Medicine (M.W., P.F., A.E.B., M.M.M., W.W., S.A., N.W., C.L.W., A.R.T.).
Sandra AbramowiczDivision of Molecular Medicine (M.W., P.F., A.E.B., M.M.M., W.W., S.A., N.W., C.L.W., A.R.T.).
Sacha la Bastide-van GemertDepartment of Epidemiology (S.l.B-v.G.), University of Groningen, University Medical Center Groningen, The Netherlands.
Nan WangDivision of Molecular Medicine (M.W., P.F., A.E.B., M.M.M., W.W., S.A., N.W., C.L.W., A.R.T.).
Carrie L WelchDivision of Molecular Medicine (M.W., P.F., A.E.B., M.M.M., W.W., S.A., N.W., C.L.W., A.R.T.).
Muredach P ReillyDivision of Cardiology (H.Z., M.P.R.), Department of Medicine, Columbia University, New York, NY.
Erik S StroesDepartment of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands (A.E.B., E.S.S.).
Kathryn J MooreDepartment of Medicine, Division of Cardiology, New York University Medical Center, NY (M.O., K.J.M.).
Alan R TallDivision of Molecular Medicine (M.W., P.F., A.E.B., M.M.M., W.W., S.A., N.W., C.L.W., A.R.T.).
Columbia University · USColumbia University Irving Medical Center · USLaboratory of Molecular Genetics · PLUniversity of Groningen · NLWelch Foundation · US

Funding

POSTDOCTORAL TRAINING IN ARTERIOSCLEROSIS RESEARCHT32HL007343 · NHLBI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI HENRY N GINSBERG, Muredach P Reilly · 1985 to 2026
$12.7M
Cholesterol efflux, CHIP and inflammasome activationR01HL107653 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ALAN richard TALL · 2011 to 2026
$7.7M
Elucidation of Tissue-Specific Transcriptomic Profiles in Cardiometabolic DiseaseR01HL113147 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO, REILLY, MUREDACH P · 2012 to 2022
$6.8M
Non-coding RNA regulation of cholesterol homeostasis and atherosclerosisR35HL135799 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MOORE, KATHRYN J · 2017 to 2023
$6.7M
Mechanisms of CD36 Signal Transduction - Resubmission - 1R01HL117334 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MOORE, KATHRYN J · 2013 to 2017
$1.9M
Mentored Patient Oriented Research in Cardiometabolic DiseaseK24HL107643 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI REILLY, MUREDACH P · 2011 to 2020
$1.4M
Becton Dickinson LSR II Analytical Flow CytometerS10RR027050 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CLYNES, RAPHAEL A. · 2011 to 2011
$413k
Macrophage-specific function of GWAS CAD-associated LIPA alleles in atherosclerosisK99HL130574 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ZHANG, HANRUI · 2016 to 2017
$272k
NCRR NIH HHS S10 RR027050NHLBI NIH HHS K24 HL107643NHLBI NIH HHS K99 HL130574NHLBI NIH HHS R01 HL107653NHLBI NIH HHS R01 HL113147NHLBI NIH HHS R01 HL117334NHLBI NIH HHS R35 HL135799NHLBI NIH HHS T32 HL007343
6 · The paper itself

Abstract

backgroundThe CANTOS trial (Canakinumab Antiinflammatory Thrombosis Outcome Study) showed that antagonism of interleukin (IL)-1β reduces coronary heart disease in patients with a previous myocardial infarction and evidence of systemic inflammation, indicating that pathways required for IL-1β secretion increase cardiovascular risk. IL-1β and IL-18 are produced via the NLRP3 inflammasome in myeloid cells in response to cholesterol accumulation, but mechanisms linking NLRP3 inflammasome activation to atherogenesis are unclear. The cholesterol transporters ATP binding cassette A1 and G1 (ABCA1/G1) mediate cholesterol efflux to high-density lipoprotein, and Abca1/g1 deficiency in myeloid cells leads to cholesterol accumulation.

methodsTo interrogate mechanisms connecting inflammasome activation with atherogenesis, we used mice with myeloid Abca1/g1 deficiency and concomitant deficiency of the inflammasome components Nlrp3 or Caspase-1/11. Bone marrow from these mice was transplanted into Ldlr

resultsMyeloid Abca1/g1 deficiency increased plasma IL-18 levels in Ldlr

conclusionsCholesterol accumulation in myeloid cells activates the NLRP3 inflammasome, which enhances neutrophil accumulation and neutrophil extracellular trap formation in atherosclerotic plaques. Patients with Tangier disease, who have increased myeloid cholesterol content, showed markers of inflammasome activation, suggesting human relevance.

Indexed as

AnimalsAtherosclerosisATP Binding Cassette Transporter 1ATP Binding Cassette Transporter, Subfamily G, Member 1Case-Control StudiesCaspase 1CaspasesCaspases, InitiatorCholesterolCytokinesDisease Models, AnimalExtracellular TrapsHumansInflammasomesInflammationMice, KnockoutAbca1 protein, mouseABCG1 protein, mouseATP Binding Cassette Transporter 1ATP Binding Cassette Transporter, Subfamily G, Member 1Casp4 protein, mouseCaspase 1CaspasesCaspases, InitiatorCholesterolCytokinesInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseReceptors, LDLatherosclerosisATP-binding cassette transporterscholesterol, HDLextracellular trapsinflammasomes

Identifiers

PMID29588315
PMCPMC6160368
OpenAlexW2795137969

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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.