ArticleCardiovascular research2023
Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages' transition into a pro-inflammatory state.
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 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Rare-Earth Nanomaterials for Advanced Theranostics of Atherosclerosis.Chemical & biomedical imaging · 2026Review
- Review
- Unraveling the molecular evolution and immune functions of Lr-CD40 in Lethenteron reissneri.Fish physiology and biochemistry · 2026Article
- Senolytic Changes in Murine Arteriovenous Fistulas with CKD.Kidney360 · 2026Article
- Platelets in systemic lupus erythematosus: from hemostatic allies to pathogenic drivers.Frontiers in immunology · 2026Review
- Research progress on macrophage regulation of atherosclerosis.Frontiers in cardiovascular medicine · 2026Review
- CD40-CD40L: a milestone in the recognition of atherosclerosis as an immune disease.Nature reviews. Cardiology · 2025Article
- Xcr1eLife · 2025Article
- Current status and challenges of multi-omics research using animal models of atherosclerosis.Journal of molecular and cellular cardiology plus · 2025Review
- LIGHT/TNFSF14 Levels in Carotid Plaques Are Associated With Symptomatic Cerebrovascular Disease.Journal of stroke · 2025Article
- The immune checkpoint regulator CD40 potentiates myocardial inflammation.Nature cardiovascular research · 2025Article
- CD40-TRAF6 inhibition suppresses cardiovascular inflammation, oxidative stress and functional complications in a mouse model of arterial hypertension.Redox biology · 2025Article
- Macrophages Unmasked: Their Pivotal Role in Driving Atherosclerosis in Systemic Lupus Erythematosus.Clinical reviews in allergy & immunology · 2025Review
- Dissecting Causal Relationship Among Immune Cells, Plasma Metabolites and Coronary Atherosclerosis: A Mendelian Randomization Study.ImmunoTargets and therapy · 2025Article
- Bufei Jiedu Formula enhances CD40 activation and macrophage polarization to eliminate intracellular MRSA persisters.Frontiers in immunology · 2025Article
- IFN-γ induced the formation of foamy macrophages via CD40 signal to controlFrontiers in immunology · 2025Article
- Identification of Novel Biomarkers Associated with Corticosteroid Resistance in Asthma by Bioinformatics Analysis and Experimental Validation.Journal of inflammation research · 2025Article
- TNF superfamily molecules in atherosclerosis: mechanistic insights and therapeutic translation.Frontiers in immunology · 2025Review
- Advancements in adoptive CAR immune cell immunotherapy synergistically combined with multimodal approaches for tumor treatment.Bioactive materials · 2024Review
- Costimulatory and Coinhibitory Immune Checkpoints in Atherosclerosis: Therapeutic Targets in Atherosclerosis?JACC. Basic to translational science · 2024Review
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsCD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis and induces a favourable stable plaque phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates atherosclerosis in hyperlipidaemic mice via macrophage-driven mechanisms. The present study aims to detail the function of myeloid CD40 in atherosclerosis using myeloid-specific CD40-deficient mice. METHOD AND
resultsCd40flox/flox and LysM-cre Cd40flox/flox mice on an Apoe-/- background were generated (CD40wt and CD40mac-/-, respectively). Atherosclerotic lesion size, as well as plaque macrophage content, was reduced in CD40mac-/- compared to CD40wt mice, and their plaques displayed a reduction in necrotic core size. Transcriptomics analysis of the CD40mac-/- atherosclerotic aorta revealed downregulated pathways of immune pathways and inflammatory responses. Loss of CD40 in macrophages changed the representation of aortic macrophage subsets. Mass cytometry analysis revealed a higher content of a subset of alternative or resident-like CD206+CD209b- macrophages in the atherosclerotic aorta of CD40mac-/- compared to CD40wt mice. RNA-sequencing of bone marrow-derived macrophages of CD40mac-/- mice demonstrated upregulation of genes associated with alternatively activated macrophages (including Folr2, Thbs1, Sdc1, and Tns1).
conclusionsWe here show that absence of CD40 signalling in myeloid cells reduces atherosclerosis and limits systemic inflammation by preventing a shift in macrophage polarization towards pro-inflammatory states. Our study confirms the merit of macrophage-targeted inhibition of CD40 as a valuable therapeutic strategy to combat atherosclerosis.
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