ArticleArteriosclerosis, thrombosis, and vascular biology2021
Endothelial HMGB1 Is a Critical Regulator of LDL Transcytosis via an SREBP2-SR-BI Axis.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- HMGB1 as a danger signal in vascular remodeling.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Review
- The role of HMGB1 in vascular endothelial cells.Apoptosis : an international journal on programmed cell death · 2026Review
- IL-6 triggers lysosomal degradation of LDL-R and enhances LDL-C uptake in vascular endothelial cells via macropinocytosis.Molecular medicine (Cambridge, Mass.) · 2026Article
- Antisense oligonucleotide inhibition of HMGB1 attenuates angiotensin II-induced abdominal aortic aneurysms.Atherosclerosis · 2025Article
- Lipid raft proteomics identify endothelial myosin-9 (MYH9) as a regulator of low-density lipoprotein transcytosis and atherosclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- HMGB1: A New Target for Ischemic Stroke and Hemorrhagic Transformation.Translational stroke research · 2025Review
- How Does HDL Participate in Atherogenesis? Antioxidant Activity Versus Role in Reverse Cholesterol Transport.Antioxidants (Basel, Switzerland) · 2025Review
- Transcytosis of LDL Across Arterial Endothelium: Mechanisms and Therapeutic Targets.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- The Role of Alarmins in the Pathogenesis of Atherosclerosis and Myocardial Infarction.Current issues in molecular biology · 2024Review
- Quinic acid regulated TMA/TMAO-related lipid metabolism and vascular endothelial function through gut microbiota to inhibit atherosclerotic.Journal of translational medicine · 2024Article
- Downregulation of HMGB1 carried by macrophage-derived extracellular vesicles delays atherosclerotic plaque formation through Caspase-11-dependent macrophage pyroptosis.Molecular medicine (Cambridge, Mass.) · 2024Article
- Reprogramming of lipid metabolism in the tumor microenvironment: a strategy for tumor immunotherapy.Lipids in health and disease · 2024Review
- Xuanfei Formula inhibited RSV infection by normalizing the SREBP2-mediated cholesterol synthesis process.Frontiers in microbiology · 2024Article
- LDL Transcytosis by the Arterial Endothelium-Atherosclerosis by a Thousand Cuts?Current atherosclerosis reports · 2023Review
- Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice.Nature cardiovascular research · 2023Article
- The potential role of scavenger receptor B type I (SR-BI) in SARS-CoV-2 infection.Immunity, inflammation and disease · 2023Review
- Oscillating Glucose Induces the Increase in Inflammatory Stress through Ninjurin-1 Up-Regulation and Stimulation of Transport Proteins in Human Endothelial Cells.Biomolecules · 2023Article
- HMGB1 is a Potential and Challenging Therapeutic Target for Parkinson's Disease.Cellular and molecular neurobiology · 2023Review
- Cardiovascular/Stroke Risk Stratification in Diabetic Foot Infection Patients Using Deep Learning-Based Artificial Intelligence: An Investigative Study.Journal of clinical medicine · 2022Review
- Role of High Mobility Group Box 1 in Cardiovascular Diseases.Inflammation · 2022Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveLDL (low-density lipoprotein) transcytosis across the endothelium is performed by the SR-BI (scavenger receptor class B type 1) receptor and contributes to atherosclerosis. HMGB1 (high mobility group box 1) is a structural protein in the nucleus that is released by cells during inflammation; extracellular HMGB1 has been implicated in advanced disease. Whether intracellular HMGB1 regulates LDL transcytosis through its nuclear functions is unknown. Approach and Results: HMGB1 was depleted by siRNA in human coronary artery endothelial cells, and transcytosis of LDL was measured by total internal reflection fluorescence microscopy. Knockdown of HMGB1 attenuated LDL transcytosis without affecting albumin transcytosis. Loss of HMGB1 resulted in reduction in SR-BI levels and depletion of SREBP2 (sterol regulatory element-binding protein 2)-a transcription factor upstream of SR-BI. The effect of HMGB1 depletion on LDL transcytosis required SR-BI and SREBP2. Overexpression of HMGB1 caused an increase in LDL transcytosis that was unaffected by inhibition of extracellular HMGB1 or depletion of RAGE (receptor for advanced glycation endproducts)-a cell surface receptor for HMGB1. The effect of HMGB1 overexpression on LDL transcytosis was prevented by knockdown of SREBP2. Loss of HMGB1 caused a reduction in the half-life of SREBP2; incubation with LDL caused a significant increase in nuclear localization of HMGB1 that was dependent on SR-BI. Animals lacking endothelial HMGB1 exhibited less acute accumulation of LDL in the aorta 30 minutes after injection and when fed a high-fat diet developed fewer fatty streaks and less atherosclerosis.
conclusionsEndothelial HMGB1 regulates LDL transcytosis by prolonging the half-life of SREBP2, enhancing SR-BI expression. Translocation of HMGB1 to the nucleus in response to LDL requires SR-BI.
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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.