Evidence map›Paper›PMID 32927275›Full record

ArticleEBioMedicine2020

Cholesterol crystals use complement to increase NLRP3 signaling pathways in coronary and carotid atherosclerosis.

Nathalie Niyonzima, Siril S Bakke, Ida Gregersen, Sverre Holm, Øystein Sandanger, Hilde L Orrem, Bjørnar Sporsheim, Liv Ryan, Xiang Yi Kong, Tuva Børresdatter Dahl and 12 more

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

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
3.7field-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

46 citing papers in PubMed, 79 citations in OpenAlex.

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  11. Atherosclerotic Plaque Crystals Induce Endothelial Dysfunction.International journal of molecular sciences · 2025
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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

22 authors at 3 institutions in 2 countries.

Nathalie NiyonzimaCentre of Molecular Inflammation Research, and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres gate 17, Trondheim 7030, Norway.
Siril S BakkeCentre of Molecular Inflammation Research, and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres gate 17, Trondheim 7030, Norway.
Ida GregersenResearch Institute of Internal Medicine, Oslo University Hospital, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
Sverre HolmResearch Institute of Internal Medicine, Oslo University Hospital, Norway.
Øystein SandangerResearch Institute of Internal Medicine, Oslo University Hospital, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
Hilde L OrremDivision of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.
Bjørnar SporsheimCentre of Molecular Inflammation Research, and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres gate 17, Trondheim 7030, Norway.
Liv RyanCentre of Molecular Inflammation Research, and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres gate 17, Trondheim 7030, Norway.
Xiang Yi KongResearch Institute of Internal Medicine, Oslo University Hospital, Norway.
Tuva Børresdatter DahlResearch Institute of Internal Medicine, Oslo University Hospital, Norway.
Mona SkjellandInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Department of Neurology, Oslo University Hospital, Norway.
Kirsten Krohg SørensenResearch Institute of Internal Medicine, Oslo University Hospital, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
Anne Mari RokstadCentre of Molecular Inflammation Research, and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres gate 17, Trondheim 7030, Norway.
Arne YndestadResearch Institute of Internal Medicine, Oslo University Hospital, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
Eicke LatzCentre of Molecular Inflammation Research, and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres gate 17, Trondheim 7030, Norway; Institute of Innate Immunity, Biomedical Center, University of Bonn, Germany.
Lars GullestadDepartment of Cardiology, Oslo University Hospital, Norway; KG Jebsen Center for Cardiac Research, and Center for Heart Failure Research, Oslo University Hospital, Norway.
Geir Ø AndersenDepartment of Cardiology, Oslo University Hospital, Norway.
Jan Kristian DamåsCentre of Molecular Inflammation Research, and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres gate 17, Trondheim 7030, Norway.
Pål AukrustResearch Institute of Internal Medicine, Oslo University Hospital, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Norway.
Tom E MollnesCentre of Molecular Inflammation Research, and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres gate 17, Trondheim 7030, Norway; Department of Immunology, Oslo University Hospital, Norway; KG Jebsen TREC, Department of Clinical Medicine, University of Tromsø, Norway; Research Laboratory, Norland Hospital, Norway.
Bente HalvorsenResearch Institute of Internal Medicine, Oslo University Hospital, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
Terje EspevikCentre of Molecular Inflammation Research, and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres gate 17, Trondheim 7030, Norway; The Central Norway Regional Health Authority, St. Olavs Hospital HF, Norway. Electronic address: terje.espevik@ntnu.no.
Oslo University Hospital · NONorwegian University of Science and Technology · NOUniversity of Bonn · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDuring atherogenesis, cholesterol precipitates into cholesterol crystals (CC) in the vessel wall, which trigger plaque inflammation by activating the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome. We investigated the relationship between CC, complement and NLRP3 in patients with cardiovascular disease.

methodsWe analysed plasma, peripheral blood mononuclear cells (PBMC) and carotid plaques from patients with advanced atherosclerosis applying ELISAs, multiplex cytokine assay, qPCR, immunohistochemistry, and gene profiling.

findingsTranscripts of interleukin (IL)-1beta(β) and NLRP3 were increased and correlated in PBMC from patients with acute coronary syndrome (ACS). Priming of these cells with complement factor 5a (C5a) and tumour necrosis factor (TNF) before incubation with CC resulted in increased IL-1β protein when compared to healthy controls. As opposed to healthy controls, systemic complement was significantly increased in patients with stable angina pectoris or ACS. In carotid plaques, complement C1q and C5b-9 complex accumulated around CC-clefts, and complement receptors C5aR1, C5aR2 and C3aR1 were higher in carotid plaques compared to control arteries. Priming human carotid plaques with C5a followed by CC incubation resulted in pronounced release of IL-1β, IL-18 and IL-1α. Additionally, mRNA profiling demonstrated that C5a and TNF priming followed by CC incubation upregulated plaque expression of NLRP3 inflammasome components.

interpretationWe demonstrate that CC are important local- and systemic complement activators, and we reveal that the interaction between CC and complement could exert its effect by activating the NLRP3 inflammasome, thus promoting the progression of atherosclerosis.

Indexed as

Signal TransductionCarotid Artery DiseasesCholesterolComplement C5aComplement System ProteinsComputational BiologyCoronary Artery DiseaseCytokinesDisease SusceptibilityGene Expression ProfilingHumansInflammasomesInflammation MediatorsLeukocytes, MononuclearLiquid CrystalsNLR Family, Pyrin Domain-Containing 3 ProteinCholesterolComplement C5aComplement System ProteinsCytokinesInflammasomesInflammation MediatorsNLR Family, Pyrin Domain-Containing 3 ProteinAtherosclerosisCarotid atherosclerosisCholesterol crystalsComplement systemCoronary artery diseaseInflammationNLRP3 inflammasome

Identifiers

PMID32927275
PMCPMC7494683
OpenAlexW3086427236

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.