ArticleCell death & disease2015
IRAK1 mediates TLR4-induced ABCA1 downregulation and lipid accumulation in VSMCs.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
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- Hypocholesterolemic agents and the gut microbiota: a review of interactions and modulatory activity.Pharmacological reports : PR · 2026Review
- Interplay Between KLF4, STAT, IRF, and NF-κB in VSMC and Macrophage Plasticity During Vascular Inflammation and Atherosclerosis.International journal of molecular sciences · 2025Review
- Bacterial Infections and Their Cell Wall Ligands Differentially Modulate Doxorubicin Sensitivity in Triple-Negative Breast Cancer Cells.Microorganisms · 2025Article
- Dehydrocostus lactone attenuates atherogenesis by promoting cholesterol efflux and inhibiting inflammation via TLR2/PPAR-γ/NF-κB signaling pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- Recent Advances in IRAK1: Pharmacological and Therapeutic Aspects.Molecules (Basel, Switzerland) · 2024Review
- Hepatoprotective effect of avicularin on lead-induced steatosis, oxidative stress, and inflammation in mice associated with the MAPK/HSP60/NLRP3 and SREBP1c pathway.Toxicology research · 2023Article
- Interleukin Receptor Associated Kinase 1 Signaling and Its Association with Cardiovascular Diseases.Reviews in cardiovascular medicine · 2022Review
- EVOO Promotes a Less Atherogenic Profile Than Sunflower Oil in Smooth Muscle Cells Through the Extracellular Vesicles Secreted by Endothelial Cells.Frontiers in nutrition · 2022Article
- Participation of ABCA1 Transporter in Pathogenesis of Chronic Obstructive Pulmonary Disease.International journal of molecular sciences · 2021Review
- Protective Effect of Joa-Gui Em through the Improvement of the NLRP3 and TLR4/NF-Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Endosomal Cholesterol in Viral Infections - A Common Denominator?Frontiers in physiology · 2021Review
- Protective Effect ofNutrients · 2020Article
- TLR4 knockout can improve dysfunction of β-cell by rebalancing proteomics disorders in pancreas of obese rats.Endocrine · 2020Article
- miR‑146a‑5p suppresses ATP‑binding cassette subfamily G member 1 dysregulation in patients with refractory Mycoplasma pneumoniae via interleukin 1 receptor‑associated kinase 1 downregulation.International journal of molecular medicine · 2019Article
- PAR2 (Protease-Activated Receptor 2) Deficiency Attenuates Atherosclerosis in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- miR-146a deficiency in hematopoietic cells is not involved in the development of atherosclerosis.PloS one · 2018Article
- Association betweenBiomedical reports · 2017Article
- The LXR ligand GW3965 inhibits Newcastle disease virus infection by affecting cholesterol homeostasis.Archives of virology · 2016Article
- Oxidized Low-Density Lipoprotein Induces Apoptosis in Cultured Neonatal Rat Cardiomyocytes by Modulating the TLR4/NF-κB Pathway.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activation of Toll-like receptor 4 (TLR4) signaling has an important role in promoting lipid accumulation and pro-inflammatory effects in vascular smooth muscle cells (VSMCs), which facilitate atherosclerosis development and progression. Previous studies have demonstrated that excess lipid accumulation in VSMCs is due to an inhibition of the expression of ATP-binding cassette transporter A1 (ABCA1), an important molecular mediator of lipid efflux from VSMCs. However, the underlying molecular mechanisms of this process are unclear. The purpose of this study was to disclose the underlying molecular mechanisms of TLR4 signaling in regulating ABCA1 expression. Primary cultured VSMCs were stimulated with 50 μg/ml oxidized low-density lipoprotein (oxLDL). We determined that enhancing TLR4 signaling using oxLDL significantly downregulated ABCA1 expression and induced lipid accumulation in VSMCs. However, TLR4 knockout significantly rescued oxLDL-induced ABCA1 downregulation and lipid accumulation. In addition, IL-1R-associated kinase 1 (IRAK1) was involved in the effects of TLR4 signaling on ABCA1 expression and lipid accumulation. Silencing IRAK1 expression using a specific siRNA reversed TLR4-induced ABCA1 downregulation and lipid accumulation in vitro. These results were further confirmed by our in vivo experiments. We determined that enhancing TLR4 signaling by administering a 12-week-long high-fat diet (HFD) to mice significantly increased IRAK1 expression, which downregulated ABCA1 expression and induced lipid accumulation. In addition, TLR4 knockout in vivo reversed the effects of the HFD on IRAK1 and ABCA1 expression, as well as on lipid accumulation. In conclusion, IRAK1 is involved in TLR4-mediated downregulation of ABCA1 expression and lipid accumulation in VSMCs.
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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.