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Cited by 65Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismLipoproteins and Cardiovascular Health

T cell cholesterol efflux suppresses apoptosis and senescence and increases atherosclerosis in middle aged mice

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Bazioti, Venetia, La Rose, Anouk M., Maassen, Sjors, Bianchi, Frans, de Boer, Rinse, Halmos, Benedek, Dabral, Deepti, Guilbaud, Emma +14 more·2022·Nature Communications
DOI 10.1038/s41467-022-31135-4PMC PMC9249754

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Abstract

ABSTRACT Atherosclerosis is a chronic inflammatory disease driven by hypercholesterolemia. During aging, T-cells accumulate cholesterol, which could lead to a pro-inflammatory phenotype. However, the role of cholesterol efflux pathways mediated by ATP-binding cassette A1 and G1 (ABCA1/ABCG1) in T-cell-dependent age-related inflammation and atherosclerosis remains poorly understood. In this study, we generated mice with T-cell-specific Abca1/Abcg1 -deficiency on the low-density-lipoprotein-receptor deficient ( Ldlr -/- ) background. T-cell Abca1/Abcg1 -deficiency decreased blood, lymph node, and splenic T-cells, and increased T-cell activation and apoptosis. T-cell Abca1/Abcg1 -deficiency induced a premature T-cell aging phenotype in middle-aged (12-13 months) Ldlr -/- mice, reflected by upregulation of senescence markers. Despite T-cell senescence and enhanced T-cell activation, T-cell Abca1/Abcg1 -deficiency decreased atherosclerosis and aortic inflammation in middle-aged Ldlr -/- mice, accompanied by decreased T-cells in atherosclerotic plaques. We attribute these effects to T-cell apoptosis downstream of T-cell activation. Collectively, T-cell cholesterol efflux pathways are critical for maintaining T-cell numbers, suppress senescence, and induce atherosclerosis in middle-aged Ldlr -/- mice.

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  • T cell specific knockout of ABCA1 and ABCG1 mice had decreased T cell numbers but increased activation, resulting in decreased atherosclerosis and aortic inflammation.

    “T cell specific knockout of ABCA1 and ABCG1 mice had decreased T cell numbers but increased activation, resulting in decreased atherosclerosis and aortic inflammation (71).”

    From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [71]

    The Results sections on peripheral T cells and activation report fewer T cells and increased activation after T cell-specific Abca1/Abcg1 deletion (page unavailable). The section on middle-aged Ldlr−/− mice reports smaller atherosclerotic lesions and changes consistent with reduced aortic inflammation, but attributes these effects primarily to increased T cell apoptosis and reduced inflammatory signaling—not increased activation. The paper also reports no change in lesion size in the other Ldlr−/− mice studied, so the claim omits an important age qualification. (LLM, conf=0.90)

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Authors
Bazioti, V., La Rose, A. M., Maassen, S., Bianchi, F., de Boer, R., Halmos, B., Dabral, D., Guilbaud, E., Flohr-Svendsen, A., Groenen, A. G., Marmolejo-Garza, A., Koster, M. H., Kloosterhuis, N. J., Havinga, R., Pranger, A. T., Langelaar-Makkinje, M., de Bruin, A., van de Sluis, B., Kohan, A. B., Yvan-Charvet, L., van den Bogaart, G., & Westerterp, M.
Affiliations
  • University Medical Center Groningen (NL)
  • University of Groningen (NL)
  • Inserm (FR)
  • University of Pittsburgh (US)
Corresponding author
Westerterp, Marit
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2022-07-01
Volume
13
Issue
1
Pages
3799-3799
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-022-31135-4
PMC
PMC9249754
OpenAlex
W4283743523
Cited by
65
References
9
Citations by year
2026: 13 · 2025: 16 · 2024: 17 · 2023: 19
FWCI
4.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Funders
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VIDI grant 917.15.350)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
ABCA1, ABCG1, T cell apoptosis, T cell senescence, atherosclerosis, age-related inflammation, hypercholesterolemia, Ldlr-deficient mice, T cell activation, aortitis, atherosclerotic plaque
MeSH terms
Animals, Biological Transport, Immunologic Deficiency Syndromes, Inflammation, T-Lymphocytes, Thymus Gland, Apoptosis, Atherosclerosis, Mice

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