ArticleNature cell biology2022
LDL delivery of microbial small RNAs drives atherosclerosis through macrophage TLR8.
Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Lipid-based nanosystems for atherosclerosis treatment: Evolving approaches and novel therapeutic strategies.Acta pharmaceutica Sinica. B · 2026Review
- Research Progress on Mesenchymal Stem Cells-Derived Small Size Vesicles for the Treatment of Liver Diseases.International journal of nanomedicine · 2026Review
- A comprehensive analysis of supermere, exomere, and extracellular vesicle isolation and cargo in colorectal cancer.Cell reports · 2025Article
- Plasminogen as a ribonucleoprotein: regulatory small RNA cargo modulates fibrinolysis and inflammation.Blood · 2025Article
- Nuclear export of transmembrane protein PROM2 is specially regulated by CRM1 and affects the sensitivity of ferroptosis in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Fortilin deficiency induces anti-atherosclerotic phenotypes in macrophages and protects hypercholesterolemic mice against atherosclerosis.Communications biology · 2025Article
- Proteomic and lipidomic analysis of low-density lipoprotein identifies potential biomarkers of early estrogen receptor-positive breast cancer.Cancer & metabolism · 2025Article
- Small RNA and Toll-like receptor interactions: origins and disease mechanisms.Trends in biochemical sciences · 2025Review
- RNase T2 deficiency promotes TLR13-dependent replenishment of tissue-protective Kupffer cells.The Journal of experimental medicine · 2025Article
- The role of 5-methylcytosine regulator-related genes in diagnostic and immune regulatory functions in atherosclerosis.Frontiers in immunology · 2025Article
- Optimized size exclusion chromatography demonstrates that extracellular vesicles are the key RNA carriers of ALK translocations in non-small cell lung cancer cell line secretome and patient plasma.Extracellular vesicles and circulating nucleic acids · 2025Article
- Extracellular vesicles and nanoparticles at a glance.Journal of cell science · 2024Review
- 5-Fluorouracil treatment represses pseudouridine-containing miRNA export into extracellular vesicles.Journal of extracellular biology · 2024Article
- Blood Lipoproteins Shape the Phenotype and Lipid Content of Early Atherosclerotic Lesion Macrophages: A Dual-Structured Mathematical Model.Bulletin of mathematical biology · 2024Article
- Lipid Toxicity in the Cardiovascular-Kidney-Metabolic Syndrome (CKMS).Biomedicines · 2024Review
- A high-cholesterol diet promotes the intravasation of breast tumor cells through an LDL-LDLR axis.Scientific reports · 2024Article
- Atherosclerotic three-layer nanomatrix vascular sheets for high-throughput therapeutic evaluation.Biomaterials · 2024Article
- Extracellular RNA in oncogenesis, metastasis and drug resistance.RNA biology · 2024Review
- Decoding the Link between Periodontitis and Neuroinflammation: The Journey of Bacterial Extracellular Vesicles.Current genomics · 2023Article
- LDL's unexpected travel partners in the road to atherosclerosis.Cardiovascular research · 2023Article
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Macrophages present a spectrum of phenotypes that mediate both the pathogenesis and resolution of atherosclerotic lesions. Inflammatory macrophage phenotypes are pro-atherogenic, but the stimulatory factors that promote these phenotypes remain incompletely defined. Here we demonstrate that microbial small RNAs (msRNA) are enriched on low-density lipoprotein (LDL) and drive pro-inflammatory macrophage polarization and cytokine secretion via activation of the RNA sensor toll-like receptor 8 (TLR8). Removal of msRNA cargo during LDL re-constitution yields particles that readily promote sterol loading but fail to stimulate inflammatory activation. Competitive antagonism of TLR8 with non-targeting locked nucleic acids was found to prevent native LDL-induced macrophage polarization in vitro, and re-organize lesion macrophage phenotypes in vivo, as determined by single-cell RNA sequencing. Critically, this was associated with reduced disease burden in distinct mouse models of atherosclerosis. These results identify LDL-msRNA as instigators of atherosclerosis-associated inflammation and support alternative functions of LDL beyond cholesterol transport.
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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.