Evidence map›Paper›PMID 39945065›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2025

Age-Related Impairments in Immune Cell Efferocytosis and Autophagy Hinder Atherosclerosis Regression.

Dominique M Boucher, Sabrina Robichaud, Victoria Lorant, Jonathan S Leon, Issraa Suliman, Adil Rasheed, Leah I Susser, Christina Emerton, Michele Geoffrion, Erica De Jong and 6 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
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

18 citing papers in PubMed.

  1. Article
  2. Review
  3. bioRxiv : the preprint server for biology · 2026
    Article
  4. The immunology behind inflammaging-causes, sources, and mechanisms.The Journal of allergy and clinical immunology · 2026
    Review
  5. Review
  6. What Do We Know About Immune System Aging from Human and Animal Studies?International journal of molecular sciences · 2026
    Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Nutrition as a systems regulator of brain aging trajectories.Frontiers in molecular neuroscience · 2026
    Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. 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

16 authors.

Dominique M BoucherDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, ON, Canada (D.M.B., S.R., V.L., I.S., A.R., L.I.S., K.J.R., M.O.).ORCID 0000-0003-2223-0117
Sabrina RobichaudDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, ON, Canada (D.M.B., S.R., V.L., I.S., A.R., L.I.S., K.J.R., M.O.).ORCID 0000-0001-5766-1094
Victoria LorantDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, ON, Canada (D.M.B., S.R., V.L., I.S., A.R., L.I.S., K.J.R., M.O.).
Jonathan S LeonUniversity of Ottawa Heart Institute, ON, Canada (D.M.B., S.R., V.L., J.S.L., I.S., A.R., L.I.S., C.E., M.G., K.J.R., M.O.).ORCID 0000-0002-0496-3782
Issraa SulimanDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, ON, Canada (D.M.B., S.R., V.L., I.S., A.R., L.I.S., K.J.R., M.O.).
Adil RasheedDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, ON, Canada (D.M.B., S.R., V.L., I.S., A.R., L.I.S., K.J.R., M.O.).ORCID 0000-0002-3204-6674
Leah I SusserDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, ON, Canada (D.M.B., S.R., V.L., I.S., A.R., L.I.S., K.J.R., M.O.).
Christina EmertonUniversity of Ottawa Heart Institute, ON, Canada (D.M.B., S.R., V.L., J.S.L., I.S., A.R., L.I.S., C.E., M.G., K.J.R., M.O.).
Michele GeoffrionUniversity of Ottawa Heart Institute, ON, Canada (D.M.B., S.R., V.L., J.S.L., I.S., A.R., L.I.S., C.E., M.G., K.J.R., M.O.).
Erica De JongMcMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada (E.D.J., D.M.E.B.).
Dawn M E BowdishMcMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada (E.D.J., D.M.E.B.).ORCID 0000-0001-6823-2957
Masanori AikawaCardiovascular Division, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences (M.A., E.A., S.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-9275-2079
Elena AikawaCardiovascular Division, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences (M.A., E.A., S.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-7835-2135
Sasha A SinghCardiovascular Division, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences (M.A., E.A., S.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0003-0929-3164
Katey J Rayner *Department of Biochemistry, Microbiology and Immunology, University of Ottawa, ON, Canada (D.M.B., S.R., V.L., I.S., A.R., L.I.S., K.J.R., M.O.).ORCID 0000-0001-6230-426X
Mireille Ouimet *Department of Biochemistry, Microbiology and Immunology, University of Ottawa, ON, Canada (D.M.B., S.R., V.L., I.S., A.R., L.I.S., K.J.R., M.O.).ORCID 0000-0002-6831-5047

Funding

Improving Mitral Compensation In Ischemic RegurgitationR01HL141917 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AIKAWA, ELENA, BISCHOFF, JOYCE E. · 2018 to 2021
$5.6M
Macrophage-derived microcalcificaitonsR01HL136431 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2017 to 2020
$2.7M
New driver of fibrosis and calcification in CAVDR01HL147095 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2019 to 2022
$2.4M
NHLBI NIH HHS R01 HL136431NHLBI NIH HHS R01 HL141917NHLBI NIH HHS R01 HL147095
6 · The paper itself

Abstract

backgroundAging is a well-established risk factor for the development and progression of atherosclerosis, but the molecular mechanisms underlying this relationship remain poorly defined, and its role in atherosclerosis regression is unknown. To uncover age-related alterations that may impair atherosclerosis regression, we investigated the response of young and old macrophages to atherogenic lipoproteins in vitro and in vivo.

methodsMetabolic and proteomic studies were performed in vitro using macrophages differentiated from the bone marrow of young or old mice. To test the role of immune cell aging in atherosclerosis regression, bone marrow from young and old donors was transplanted into irradiated young recipient mice expressing gain-of-function AAV-PCSK9 (adeno-associated virus-proprotein convertase subtilisin/kexin type 9). Following 14 weeks of Western diet feeding, atherosclerosis regression was induced by switching to a standard laboratory diet for 4 weeks.

resultsCompared with young macrophages, old macrophages accumulated more lipid droplets upon lipid loading with the pro-atherogenic lipoprotein aggregated LDL (low-density lipoprotein), accompanied by a failure to proportionally induce autophagy and cholesterol efflux. Proteomic analysis of bone marrow-derived macrophages revealed that pathways related to endocytosis, engulfment, and phagocytosis were downregulated in old lipid-loaded macrophages. Functional studies confirmed a reduction in efferocytic capacity in old macrophages. In recipient mice transplanted with old bone marrow, atherosclerosis regression was impaired, as evidenced by inefficient resolution of circulating inflammatory cell levels, reduced activation of plaque autophagy and apoptotic cell clearance, and persistent plaque CD45

conclusionsAging impairs macrophage function through reduced efferocytosis and autophagy activation, limiting atherosclerosis regression. These results highlight the need to better define the mechanisms linking aging to atherosclerosis to develop targeted therapies for the aging population.

Indexed as

AgingAortic DiseasesAtherosclerosisAutophagyMacrophagesPhagocytosisAge FactorsAnimalsBone Marrow TransplantationCells, CulturedCellular SenescenceDiet, WesternDisease Models, AnimalEfferocytosisMaleMicePcsk9 protein, mouseProprotein Convertase 9atherosclerosiscellular senescencelipoproteins, LDLmacrophagesphagocytosisplaque, atherosclerotic

Identifiers

PMID39945065
PMCPMC11936474

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