ArticlePloS one2013
Polyoxygenated cholesterol ester hydroperoxide activates TLR4 and SYK dependent signaling in macrophages.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The trial behind it
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- Acute and long-term effect of percutaneous coronary intervention on serially-measured oxidative, inflammatory, and coagulation biomarkers in patients with stable angina.Journal of thrombosis and thrombolysis · 2016Trial
- Relationship of oxidized phospholipids on apolipoprotein B-100 to cardiovascular outcomes in patients treated with intensive versus moderate atorvastatin therapy: the TNT trial.Journal of the American College of Cardiology · 2015Trial
- From damage signals to immune modulators: oxidized lipids in immunometabolic inflammation.Journal of lipid research · 2026Review
- Sustained monocyte activation by persistent challenges with either oxLDL or free cholesterol and underlying mechanisms.ImmunoHorizons · 2026Article
- Myeloid ACAT1/SOAT1: a novel regulator of dyslipidemia and retinal neovascularization.npj metabolic health and disease · 2025Review
- Article
- Modulation of endothelium function by fatty acids.Molecular and cellular biochemistry · 2022Review
- Recognition of Oxidized Lipids by Macrophages and Its Role in Atherosclerosis Development.Biomedicines · 2021Review
- Article
- From Inert Storage to Biological Activity-In Search of Identity for Oxidized Cholesteryl Esters.Frontiers in endocrinology · 2020Review
- TLR4 (Toll-Like Receptor 4)-Dependent Signaling Drives Extracellular Catabolism of LDL (Low-Density Lipoprotein) Aggregates.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- A monoclonal antibody to assess oxidized cholesteryl esters associated with apoAI and apoB-100 lipoproteins in human plasma.Journal of lipid research · 2019Article
- Endogenous cholesterol ester hydroperoxides modulate cholesterol levels and inhibit cholesterol uptake in hepatocytes and macrophages.Redox biology · 2019Article
- Inhibition of Neuroinflammation by AIBP: Spinal Effects upon Facilitated Pain States.Cell reports · 2018Article
- Palmitate and minimally-modified low-density lipoprotein cooperatively promote inflammatory responses in macrophages.PloS one · 2018Article
- Lipid and Non-lipid Factors Affecting Macrophage Dysfunction and Inflammation in Atherosclerosis.Frontiers in physiology · 2018Review
- The effect of oxidized phospholipids on phenotypic polarization and function of macrophages.Free radical biology & medicine · 2017Review
- Comprehensive metabolomics identified lipid peroxidation as a prominent feature in human plasma of patients with coronary heart diseases.Redox biology · 2017Article
- Screening of potential gene markers for predicting carotid atheroma plaque formation using bioinformatics approaches.Molecular medicine reports · 2017Article
- Oxidized cholesteryl esters and inflammation.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Oxidation of low-density lipoprotein (LDL) is one of the major causative mechanisms in the development of atherosclerosis. In previous studies, we showed that minimally oxidized LDL (mmLDL) induced inflammatory responses in macrophages, macropinocytosis and intracellular lipid accumulation and that oxidized cholesterol esters (OxCEs) were biologically active components of mmLDL. Here we identified a specific OxCE molecule responsible for the biological activity of mmLDL and characterized signaling pathways in macrophages in response to this OxCE. Using liquid chromatography - tandem mass spectrometry and biological assays, we identified an oxidized cholesteryl arachidonate with bicyclic endoperoxide and hydroperoxide groups (BEP-CE) as a specific OxCE that activates macrophages in a TLR4/MD-2-dependent manner. BEP-CE induced TLR4/MD-2 binding and TLR4 dimerization, phosphorylation of SYK, ERK1/2, JNK and c-Jun, cell spreading and uptake of dextran and native LDL by macrophages. The enhanced macropinocytosis resulted in intracellular lipid accumulation and macrophage foam cell formation. Bone marrow-derived macrophages isolated from TLR4 and SYK knockout mice did not respond to BEP-CE. The presence of BEP-CE was demonstrated in human plasma and in the human plaque material captured in distal protection devices during percutaneous intervention. Our results suggest that BEP-CE is an endogenous ligand that activates the TLR4/SYK signaling pathway. Because BEP-CE is present in human plasma and human atherosclerotic lesions, BEP-CE-induced and TLR4/SYK-mediated macrophage responses may contribute to chronic inflammation in human atherosclerosis.
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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.