Evidence map›Paper›PMID 37390467›Full record

ArticleCardiovascular research2023

Single-cell profiling reveals age-associated immunity in atherosclerosis.

Virginia Smit, Jill de Mol, Frank H Schaftenaar, Marie A C Depuydt, Rimke J Postel, Diede Smeets, Fenne W M Verheijen, Laurens Bogers, Janine van Duijn, Robin A F Verwilligen and 15 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
9.4field-weighted citation impact, top 2% 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

52 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
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  4. Screening for candidate genes and cell populations associated with atherosclerotic calcification using single-cell RNA sequencing.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
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  20. Rodent Models for Atherosclerosis.International journal of molecular sciences · 2025
    Review
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

25 authors at 5 institutions in 3 countries.

Virginia SmitLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.ORCID 0000-0003-1181-3122
Jill de MolLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Frank H SchaftenaarLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Marie A C DepuydtLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Rimke J PostelLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Diede SmeetsLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Fenne W M VerheijenLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Laurens BogersLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Janine van DuijnLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Robin A F VerwilligenLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Hendrika W GrievinkLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Mireia N A Bernabé KleijnLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Eva van IngenLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Maaike J M de JongLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Lauren GoncalvesDepartment of Surgery, Haaglanden Medical Center-location Westeinde, Lijnbaan 32, 2515 VA The Hague, The Netherlands.
Judith A H M PeetersDepartment of Surgery, Haaglanden Medical Center-location Westeinde, Lijnbaan 32, 2515 VA The Hague, The Netherlands.
Harm J SmeetsDepartment of Surgery, Haaglanden Medical Center-location Westeinde, Lijnbaan 32, 2515 VA The Hague, The Netherlands.
Anouk WezelDepartment of Surgery, Haaglanden Medical Center-location Westeinde, Lijnbaan 32, 2515 VA The Hague, The Netherlands.
Julia K PolanskyBerlin Institute of Health at Charité-Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Augustenburger Platz 1, 13353 Berlin, Germany.
Menno P J de WintherAmsterdam University Medical Centers-location AMC, University of Amsterdam, Experimental Vascular Biology, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Christoph J BinderDepartment of Laboratory Medicine, Medical University of Vienna, Lazarettgasse 14, AKH BT25.2, 1090 Vienna, Austria.
Dimitrios TsiantoulasDepartment of Laboratory Medicine, Medical University of Vienna, Lazarettgasse 14, AKH BT25.2, 1090 Vienna, Austria.
Ilze BotLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Johan KuiperLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.ORCID 0000-0001-5834-690X
Amanda C FoksLeiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.ORCID 0000-0002-9747-3458
Leiden University · NLMedisch Centrum Haaglanden · NLMedical University of Vienna · ATAmsterdam University Medical Centers · NLBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DE

Funding

Austrian Science Fund I4647Austrian Science Fund FWF I 4647Dutch Heart Foundation 2018T051ERA-CVD B-eatATHERO consortiumLeducq Foundation TNE-20CVD03
6 · The paper itself

Abstract

aimsAging is a dominant driver of atherosclerosis and induces a series of immunological alterations, called immunosenescence. Given the demographic shift towards elderly, elucidating the unknown impact of aging on the immunological landscape in atherosclerosis is highly relevant. While the young Western diet-fed Ldlr-deficient (Ldlr-/-) mouse is a widely used model to study atherosclerosis, it does not reflect the gradual plaque progression in the context of an aging immune system as occurs in humans. METHODS AND

resultsHere, we show that aging promotes advanced atherosclerosis in chow diet-fed Ldlr-/- mice, with increased incidence of calcification and cholesterol crystals. We observed systemic immunosenescence, including myeloid skewing and T-cells with more extreme effector phenotypes. Using a combination of single-cell RNA-sequencing and flow cytometry on aortic leucocytes of young vs. aged Ldlr-/- mice, we show age-related shifts in expression of genes involved in atherogenic processes, such as cellular activation and cytokine production. We identified age-associated cells with pro-inflammatory features, including GzmK+CD8+ T-cells and previously in atherosclerosis undefined CD11b+CD11c+T-bet+ age-associated B-cells (ABCs). ABCs of Ldlr-/- mice showed high expression of genes involved in plasma cell differentiation, co-stimulation, and antigen presentation. In vitro studies supported that ABCs are highly potent antigen-presenting cells. In cardiovascular disease patients, we confirmed the presence of these age-associated T- and B-cells in atherosclerotic plaques and blood.

conclusionsCollectively, we are the first to provide comprehensive profiling of aged immunity in atherosclerotic mice and reveal the emergence of age-associated T- and B-cells in the atherosclerotic aorta. Further research into age-associated immunity may contribute to novel diagnostic and therapeutic tools to combat cardiovascular disease.

Indexed as

Aortic DiseasesAtherosclerosisCardiovascular DiseasesPlaque, AtheroscleroticAgedAnimalsDisease Models, AnimalHumansLeukocytesMiceMice, Inbred C57BLMice, KnockoutReceptors, LDLReceptors, LDLAgingAtherosclerosisCardiovascular diseaseImmunologyImmunosenescence

Identifiers

PMID37390467
PMCPMC10676459
OpenAlexW4382653974

What OpenQuestion holds

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LicenceCC BY-NC
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.