ArticleCardiovascular research2023
Cholesterol accumulation in macrophages drives NETosis in atherosclerotic plaques via IL-1β secretion.
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 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Neutrophil extracellular traps (NETs) and NETosis in alcohol-associated diseases: A systematic review.Alcohol, clinical & experimental research · 2025Pooled it
- Integrative transcriptomic and machine learning analysis identifies PYCARD and IFI30 as immune-lysosomal biomarkers of ANCA-associated glomerulonephritis.Renal failure · 2026Article
- Macrophage ACAT1 Aggravates Alcohol-Associated Liver Disease by Inducing Mitochondrial Damage and NLRP3 Activation.Journal of gastroenterology and hepatology · 2026Article
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- Lactate-Primed NETosis Modulates Hepatic Regeneration During Acute Liver Failure via the TLR9/KLF15/AJUBA Axis.Cell proliferation · 2026Article
- Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks.International journal of molecular sciences · 2026Review
- Therapeutic mechanisms of umbilical cord mesenchymal stem cell-derived exosomes in ischemic stroke: A transcriptomic and metabolomic study.Neural regeneration research · 2026Article
- Postoperative Stress Accelerates Atherosclerosis Through Inflammatory Remodeling of the HDL Proteome and Impaired Reverse Cholesterol Transport.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lipid droplet-associated proteins: Roles in cardiovascular diseases.Journal of lipid research · 2026Review
- Pleuromutilins Suppress Hepatocellular Carcinoma Growth via ABCA1 Inhibition-Induced Cholesterol Accumulation.Cancers · 2026Article
- The Interaction of Neutrophil Extracellular Traps and Complement in Intracerebral Hemorrhage.Cellular and molecular neurobiology · 2026Review
- Aggressive cholesterol lowering normalizes atherosclerosis regression in Jak2Journal of lipid research · 2026Article
- The association of neutrophil-lymphocyte ratio with stroke recurrence in patients with symptomatic nonacute atherosclerotic internal carotid artery occlusion.Quantitative imaging in medicine and surgery · 2026Article
- Assessment of N/L ratio and subclinical atherosclerosis in FH subjects with or without LDLR mutation.Journal of the Endocrine Society · 2026Article
- Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026Review
- A pathology-to-single-cell framework links SPP1Journal of translational medicine · 2026Article
- Neutrophils as critical orchestrators of chronic inflammation.Cellular & molecular immunology · 2026Review
- Decoding the crosstalk: interplay between macrophage programmed cell death networks and cholesterol efflux.Frontiers in cardiovascular medicine · 2026Review
- 3-Hydroxystearic acid promotes cholesterol efflux and attenuates atherosclerosis via the ALKBH5/PAX-8/ABCA1 pathway.Frontiers in immunology · 2026Article
- Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
aimsNeutrophil extracellular trap formation (NETosis) increases atherosclerotic plaque vulnerability and athero-thrombosis. However, mechanisms promoting NETosis during atherogenesis are poorly understood. We have shown that cholesterol accumulation due to myeloid cell deficiency of the cholesterol transporters ATP Binding Cassette A1 and G1 (ABCA1/G1) promotes NLRP3 inflammasome activation in macrophages and neutrophils and induces prominent NETosis in atherosclerotic plaques. We investigated whether NETosis is a cell-intrinsic effect in neutrophils or is mediated indirectly by cellular crosstalk from macrophages to neutrophils involving IL-1β. METHODS AND
resultsWe generated mice with neutrophil or macrophage-specific Abca1/g1 deficiency (S100A8CreAbca1fl/flAbcg1fl/fl or CX3CR1CreAbca1fl/flAbcg1fl/fl mice, respectively), and transplanted their bone marrow into low-density lipoprotein receptor knockout mice. We then fed the mice a cholesterol-rich diet. Macrophage, but not neutrophil Abca1/g1 deficiency activated inflammasomes in macrophages and neutrophils, reflected by caspase-1 cleavage, and induced NETosis in plaques. NETosis was suppressed by administering an interleukin (IL)-1β neutralizing antibody. The extent of NETosis in plaques correlated strongly with the degree of neutrophil accumulation, irrespective of blood neutrophil counts, and neutrophil accumulation was decreased by IL-1β antagonism. In vitro, IL-1β or media transferred from Abca1/g1-deficient macrophages increased NETosis in both control and Abca1/Abcg1 deficient neutrophils. This cell-extrinsic effect of IL-1β on NETosis was blocked by an NLRP3 inhibitor.
conclusionThese studies establish a new link between inflammasome-mediated IL-1β production in macrophages and NETosis in atherosclerotic plaques. Macrophage-derived IL-1β appears to increase NETosis both by increasing neutrophil recruitment to plaques and by promoting neutrophil NLRP3 inflammasome activation.
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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.