Evidence map›Paper›PMID 34255973›Full record

ArticleCirculation2021

Hyperglycemia Induces Trained Immunity in Macrophages and Their Precursors and Promotes Atherosclerosis.

Laurienne Edgar, Naveed Akbar, Adam T Braithwaite, Thomas Krausgruber, Héctor Gallart-Ayala, Jade Bailey, Alastair L Corbin, Tariq E Khoyratty, Joshua T Chai, Mohammad Alkhalil and 16 more

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

Article in Circulation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers.

0numbers the graph read from it
0cells of the map it votes in
209citing papers in PubMed
14.4field-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

209 citing papers in PubMed, 283 citations in OpenAlex.

  1. Review
  2. Article
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  8. Innate Immune Memory Responses in Organ Transplantation.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Innate immunity: current understandings and future perspectives.Signal transduction and targeted therapy · 2026
    Review
  14. Stress Hyperglycemia Drives CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  15. Myeloid Cell-Specific Deletion of LGR4 Suppresses Atherosclerotic Lesion Formation.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Article
  16. Toward a Future Where Diabetes No Longer Limits Mesh Surgery.International urogynecology journal · 2026
    Article
  17. Review
  18. Article
  19. Article
  20. Review

149 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 7 institutions in 6 countries.

Laurienne Edgar *Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).ORCID 0000-0001-7893-2324
Naveed Akbar *Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).ORCID 0000-0003-4620-6373
Adam T BraithwaiteDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).ORCID 0000-0003-3228-2172
Thomas KrausgruberCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (T.K., A.F.R., C.B.).ORCID 0000-0002-1374-0329
Héctor Gallart-AyalaDivision of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (H.G.-A., C.E.W.).
Jade BaileyDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).
Alastair L CorbinThe Kennedy Institute of Rheumatology, University of Oxford, UK (A.L.C., T.E.K., I.A.U.).ORCID 0000-0001-7308-9286
Tariq E KhoyrattyThe Kennedy Institute of Rheumatology, University of Oxford, UK (A.L.C., T.E.K., I.A.U.).ORCID 0000-0001-5911-0026
Joshua T ChaiDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).
Mohammad AlkhalilDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).ORCID 0000-0002-3088-8878
André F RendeiroCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (T.K., A.F.R., C.B.).ORCID 0000-0001-9362-5373
Klemen ZibernaDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).ORCID 0000-0003-3819-3779
Ritu AryaDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).
Thomas J CahillDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).
Christoph BockCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (T.K., A.F.R., C.B.).ORCID 0000-0001-6091-3088
Jurga LaurencikieneDepartment of Medicine (H7) (J.L., M.R.), Karolinska University Hospital, Stockholm, Sweden.
Mark J CrabtreeDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).ORCID 0000-0003-3298-2697
Madeleine E LemieuxBioinfo, Plantagenet, ON, Canada (M.E.L.).
Niels P RiksenDepartment of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands (N.P.R.., M.G.N.).ORCID 0000-0001-9197-8124
Mihai G NeteaDepartment of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands (N.P.R.., M.G.N.).
Craig E WheelockDivision of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (H.G.-A., C.E.W.).
Keith M ChannonDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).
Mikael RydénDepartment of Medicine (H7) (J.L., M.R.), Karolinska University Hospital, Stockholm, Sweden.
Irina A UdalovaThe Kennedy Institute of Rheumatology, University of Oxford, UK (A.L.C., T.E.K., I.A.U.).
Ricardo CarnicerDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).ORCID 0000-0002-7440-2964
Robin P ChoudhuryDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK (L.E., N.A., A.T.B., J.B., J.T.C., M.A., K.Z., R.A., T.J.C., M.J.C., K.M.C., R.C., R.P.C.).ORCID 0000-0002-8046-1688
Anna Needs Neuroblastoma Answers · USKarolinska University Hospital · SEKennedy Center · DKCeMM Research Center for Molecular Medicine · ATAustrian Research Institute for Artificial Intelligence · ATRadboud University Nijmegen · NLUniversity of Bonn · DE

Funding

British Heart Foundation CH/16/1/32013British Heart Foundation FS/14/56/31049British Heart Foundation PG/18/53/33895British Heart Foundation RE/13/1/30181Medical Research Council G0900747 91070Wellcome Trust 090532/Z/09/Z
6 · The paper itself

Abstract

backgroundCardiovascular risk in diabetes remains elevated despite glucose-lowering therapies. We hypothesized that hyperglycemia induces trained immunity in macrophages, promoting persistent proatherogenic characteristics.

methodsBone marrow-derived macrophages from control mice and mice with diabetes were grown in physiological glucose (5 mmol/L) and subjected to RNA sequencing (n=6), assay for transposase accessible chromatin sequencing (n=6), and chromatin immunoprecipitation sequencing (n=6) for determination of hyperglycemia-induced trained immunity. Bone marrow transplantation from mice with (n=9) or without (n=6) diabetes into (normoglycemic)

resultsIn macrophages, high extracellular glucose promoted proinflammatory gene expression and proatherogenic functional characteristics through glycolysis-dependent mechanisms. Bone marrow-derived macrophages from diabetic mice retained these characteristics, even when cultured in physiological glucose, indicating hyperglycemia-induced trained immunity. Bone marrow transplantation from diabetic mice into (normoglycemic)

conclusionsHyperglycemia-induced trained immunity may explain why targeting elevated glucose is ineffective in reducing macrovascular risk in diabetes and suggests new targets for disease prevention and therapy.

Indexed as

AnimalsAtherosclerosisCells, CulturedDiabetes Mellitus, ExperimentalEndarterectomy, CarotidHumansHyperglycemiaImmunity, CellularLeukocytes, MononuclearMacrophagesMiceMice, 129 StrainMice, Transgenicdiabetes mellitusepigeneticsglucoseinflammationmacrophages

Identifiers

PMID34255973
PMCPMC8448412
OpenAlexW3179782779

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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.