ArticleThe Journal of biological chemistry
Macrophages bind LDL using heparan sulfate and the perlecan protein core.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Could chimeric antigen receptor-T cell treatment of atherosclerosis in mice translate to a human therapy?Annals of translational medicine · 2026Article
- Immune cells regulate circulating adipocyte extracellular vesicle levels in response to metabolic shifts.Cell metabolism · 2026Article
- Heparan Sulfate Proteoglycans in Immunity.Proteoglycan research · 2026Article
- Xylosyltransferase-II deficiency rewires innate immune signaling and destabilizes polarization in human macrophages.Frontiers in immunology · 2026Article
- Applications of Surface Plasmon Resonance in Heparan Sulfate Interactome Research.Biomedicines · 2025Review
- Extracellular matrix in vascular homeostasis and disease.Nature reviews. Cardiology · 2025Review
- Proteomic and lipidomic analysis of low-density lipoprotein identifies potential biomarkers of early estrogen receptor-positive breast cancer.Cancer & metabolism · 2025Article
- The extracellular heparan sulfatase SULF2 limits myeloid IFNβ signaling and Th17 responses in inflammatory arthritis.Cellular and molecular life sciences : CMLS · 2024Article
- Plasma glycocalyx pattern: a mirror of endothelial damage in chronic kidney disease.Clinical kidney journal · 2023Article
- Unravelling the limb regeneration mechanisms of Polypedates maculatus, a sub-tropical frog, by transcriptomics.BMC genomics · 2023Article
- Pentosan Polysulfate Affords Pleotropic Protection to Multiple Cells and Tissues.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The Human Myofibroblast Marker Xylosyltransferase-I: A New Indicator for Macrophage Polarization.Biomedicines · 2022Article
- TNF-α Inhibitors in Combination with MTX Reduce Circulating Levels of Heparan Sulfate/Heparin and Endothelial Dysfunction Biomarkers (sVCAM-1, MCP-1, MMP-9 and ADMA) in Women with Rheumatoid Arthritis.Journal of clinical medicine · 2022Article
- Unusual Association of NF-κB Components in Tumor-Associated Macrophages (TAMs) Promotes HSPG2-Mediated Immune-Escaping Mechanism in Breast Cancer.International journal of molecular sciences · 2022Article
- Smooth Muscle Cell-Macrophage Interactions Leading to Foam Cell Formation in Atherosclerosis: Location, Location, Location.Frontiers in physiology · 2022Review
- Perlecan, A Multi-Functional, Cell-Instructive, Matrix-Stabilizing Proteoglycan With Roles in Tissue Development Has Relevance to Connective Tissue Repair and Regeneration.Frontiers in cell and developmental biology · 2022Review
- Catalpol Inhibits Macrophage Polarization and Prevents Postmenopausal Atherosclerosis Through Regulating Estrogen Receptor Alpha.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The retention of low-density lipoprotein (LDL) is a key process in the pathogenesis of atherosclerosis and largely mediated via smooth-muscle cell-derived extracellular proteoglycans including the glycosaminoglycan chains. Macrophages can also internalize lipids via complexes with proteoglycans. However, the role of polarized macrophage-derived proteoglycans in binding LDL is unknown and important to advance our understanding of the pathogenesis of atherosclerosis. We therefore examined the identity of proteoglycans, including the pendent glycosaminoglycans, produced by polarized macrophages to gain insight into the molecular basis for LDL binding. Using the quartz crystal microbalance with dissipation monitoring technique, we established that classically activated macrophage (M1)- and alternatively activated macrophage (M2)-derived proteoglycans bind LDL via both the protein core and heparan sulfate (HS) in vitro. Among the proteoglycans secreted by macrophages, we found perlecan was the major protein core that bound LDL. In addition, we identified perlecan in the necrotic core as well as the fibrous cap of advanced human atherosclerotic lesions in the same regions as HS and colocalized with M2 macrophages, suggesting a functional role in lipid retention in vivo. These findings suggest that macrophages may contribute to LDL retention in the plaque by the production of proteoglycans; however, their contribution likely depends on both their phenotype within the plaque and the presence of enzymes, such as heparanase, that alter the secreted protein structure.
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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.