ArticlePloS one2010
Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03726645 (The Role of Gut Microbiota in the Pathogenesis of Ankylosing Spondylitis), which is not on this map. Cited by 509 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
The Role of Gut Microbiota in the Pathogenesis of Ankylosing Spondylitis (AS), and the Effect of Fecal Microbiota Transplantation on Gut Microbiota, Gut Wall Inflammation and Clinical Activity of AS
Who cites it
509 citing papers in PubMed, 1 synthesis or guideline pooled it, 996 citations in OpenAlex.
- Colchicine may become a new cornerstone therapy for coronary artery disease: a meta-analysis of randomized controlled trials.Clinical rheumatology · 2022Pooled it
- Lipid droplets as redox-active organelles after spinal cord injury: lipid peroxidation, mitochondrial dysfunction, and neuroinflammation.Redox report : communications in free radical research · 2026Review
- NLRP3 inflammasome activation by particles and fibers: implications for human hazard assessment.Archives of toxicology · 2026Review
- Molecular Mapping of Atherosclerotic Plaques with MALDI Mass Spectrometry Imaging.International journal of molecular sciences · 2026Review
- Article
- Red Blood Cell Distribution Width Is a Biomarker of Red Cell Dysfunction Associated with Inflammation, Macrophage Polarization, and Coronary Artery Calcification: A Prognostic Marker in Cardiovascular Disease and a Potential Target for Anti-Cytokine Therapy.Life (Basel, Switzerland) · 2026Review
- Mitochondrial Redox Failure Links Senescence-like Foam Cell Stress to Ferroptosis and Plaque Non-Resolution in Atherosclerosis.Antioxidants (Basel, Switzerland) · 2026Review
- Residual Atherothrombotic Risk After Myocardial Infarction: Integrating Lipid, Inflammatory and Thrombotic Pathways.Journal of clinical medicine · 2026Review
- Altered cholesterol immunometabolism activates the macrophage NLRP3-inflammasome in lung fibrosis.American journal of respiratory cell and molecular biology · 2026Article
- Disruption of upstream ox-LDL signaling and HSP90-mediated NLRP3 stability protects against experimental steatohepatitis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Inflammation and Immune Mediators in the Context of Atherosclerotic Cardiovascular Disease and Percutaneous Coronary Intervention: Implications for Therapeutics.Medical sciences (Basel, Switzerland) · 2026Review
- PCSK9 in critical illness - It's not all about lipids.Annals of clinical biochemistry · 2026Review
- Inflammatory factors and hypertensive nephropathy: A bidirectional 2-sample Mendelian randomization study.Medicine · 2026Article
- Mechanisms and therapeutic potential of colchicine in atherosclerotic cardiovascular disease.Nature cardiovascular research · 2026Review
- Lipopolysaccharides Drive Proinflammatory Extracellular Vesicle Secretion in Coronary Artery Endothelial Cells via Noncanonical Inflammasome Activation.Cellular and molecular life sciences : CMLS · 2026Article
- A broad cathepsin inhibitor blocks crystal-stimulated inflammasome-dependent and -independent inflammation and gout arthritis.Communications medicine · 2026Article
- Cholesterol-rich diet exacerbates steatohepatitis in the STAM mouse model.Scientific reports · 2026Article
- Retinal phenotype of APOB100 transgenic mice on a Western diet with human-like hyperlipidemia and cholesterol crystals in the retina and choroid.Lab animal · 2026Article
- From damage signals to immune modulators: oxidized lipids in immunometabolic inflammation.Journal of lipid research · 2026Review
- The NLRP3 Inflammasome: Mechanisms of Activation, Regulation, and Therapeutic Opportunities.MedComm · 2026Review
449 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChronic inflammation of the arterial wall is a key element in the pathogenesis of atherosclerosis, yet the factors that trigger and sustain the inflammation remain elusive. Inflammasomes are cytoplasmic caspase-1-activating protein complexes that promote maturation and secretion of the proinflammatory cytokines interleukin(IL)-1beta and IL-18. The most intensively studied inflammasome, NLRP3 inflammasome, is activated by diverse substances, including crystalline and particulate materials. As cholesterol crystals are abundant in atherosclerotic lesions, and IL-1beta has been linked to atherogenesis, we explored the possibility that cholesterol crystals promote inflammation by activating the inflammasome pathway. PRINCIPAL
findingsHere we show that human macrophages avidly phagocytose cholesterol crystals and store the ingested cholesterol as cholesteryl esters. Importantly, cholesterol crystals induced dose-dependent secretion of mature IL-1beta from human monocytes and macrophages. The cholesterol crystal-induced secretion of IL-1beta was caspase-1-dependent, suggesting the involvement of an inflammasome-mediated pathway. Silencing of the NLRP3 receptor, the crucial component in NLRP3 inflammasome, completely abolished crystal-induced IL-1beta secretion, thus identifying NLRP3 inflammasome as the cholesterol crystal-responsive element in macrophages. The crystals were shown to induce leakage of the lysosomal protease cathepsin B into the cytoplasm and inhibition of this enzyme reduced cholesterol crystal-induced IL-1beta secretion, suggesting that NLRP3 inflammasome activation occurred via lysosomal destabilization.
conclusionsThe cholesterol crystal-induced inflammasome activation in macrophages may represent an important link between cholesterol metabolism and inflammation in atherosclerotic lesions.
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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.