ArticleArteriosclerosis, thrombosis, and vascular biology2024
Trem2 Agonist Reprograms Foamy Macrophages to Promote Atherosclerotic Plaque Stability-Brief Report.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 46 citations in OpenAlex.
- Ilexoside K Ameliorates Atherosclerosis by Suppressing CD72Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cell-Surface Signatures and Targets of Modulated Vascular Smooth Muscle Cells in Atherosclerosis: From State Identification to Precision Intervention.Journal of cardiovascular development and disease · 2026Review
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Soluble TREM2: Biomarker, Bystander, or Causal Mediator in Atherosclerosis?Circulation research · 2026Article
- Reprogramming macrophage metabolism for cardiovascular therapy: From molecular pathways to precision nanomedicine.Materials today. Bio · 2026Review
- S100A8/A9 and S100A12 Proteins and Macrophage Polarization: Therapeutic Targets in Atherosclerosis.Biomolecules · 2026Review
- Carotid plaque macrophage burden and inflammatory lipid-associated macrophage markers predict secondary major adverse cardiovascular events after endarterectomy.European heart journal · 2026Article
- Article
- [Dual role and therapeutic potential of TREM2 in atherosclerosis].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Adrenal Gland Macrophage-derived TGF-β Governs Vascular Permeability to Drive Monocyte Recruitment during Stress.bioRxiv : the preprint server for biology · 2026Article
- From lipoprotein metabolism to blood clotting: Highlights of the 2025 Fredrickson lipid research conference.Journal of lipid research · 2026Article
- Diabetes-induced TREM2-endothelial cell signaling impairs ischemic vascular repair.Science translational medicine · 2026Article
- Triggering receptor expressed on myeloid cell family in atherosclerosis: from mechanisms to intervention strategies.Cell communication and signaling : CCS · 2026Review
- Aggressive cholesterol lowering normalizes atherosclerosis regression in Jak2Journal of lipid research · 2026Article
- Macrophages in human atherosclerotic plaques in the era of single-cell and spatial transcriptomics.ImmunoHorizons · 2026Review
- Review
- TREM2: A Potential Target for the Targeted Therapy of Metabolic Diseases.Mediators of inflammation · 2026Review
- The TREM2 paradox in fibrosis: a unified mechanism for opposite outcomes across organs.Frontiers in immunology · 2026Review
- CD4Frontiers in immunology · 2026Review
- Revisiting TREM2: from multi-omics signaling networks to clinical translation.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundTrem2 (triggering receptor on myeloid cells 2), a surface lipid receptor, is expressed on foamy macrophages within atherosclerotic lesions and regulates cell survival, proliferation, and anti-inflammatory responses. Studies examining the role of Trem2 in atherosclerosis have shown that deletion of Trem2 leads to impaired foamy macrophage lipid uptake, proliferation, survival, and cholesterol efflux. Thus, we tested the hypothesis that administration of a Trem2 agonist antibody (AL002a) to atherogenic mice would enhance macrophage survival and decrease necrotic core formation to improve plaque stability.
methodsTo model a therapeutic intervention approach, atherosclerosis-prone mice (Ldlr [low-density lipoprotein receptor]
resultsAL002a-treated mice had increased lesion size in both the aortic root and whole mount aorta, which correlated with an expansion of plaque macrophage area. This expansion was due to increased macrophage survival and proliferation in plaques. Importantly, plaques from AL002a-treated mice showed improved features of plaque stability, including smaller necrotic cores, increased fibrous caps, and greater collagen deposition. Single-cell RNA sequencing of whole aorta suspensions from isotype- and AL002a-treated atherosclerotic mice revealed that Trem2 agonism dramatically altered foamy macrophage transcriptome. This included upregulation of oxidative phosphorylation and increased expression of collagen genes. In vitro studies validated that Trem2 agonism with AL002a promoted foamy macrophage oxidized low-density lipoprotein uptake, survival, and cholesterol efflux.
conclusionsTrem2 agonism expands atherosclerotic plaque macrophages by promoting cell survival and proliferation but improves features of plaque stability by rewiring foamy macrophage function to enhance cholesterol efflux and collagen deposition.
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Registered trials
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.