Macrophages bind LDL using heparan sulfate and the perlecan protein core
| Autor: | John M. Whitelock, Megan S. Lord, Ha Na Kim, Helen Williams, Heather J. Medbury, Chun-yi Ng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
PMA phorbol-12-myristate 13-acetate extracellular matrix HS heparan sulfate Perlecan macrophage Biochemistry Glycosaminoglycan Extracellular matrix CS chondroitin sulfate 03 medical and health sciences chemistry.chemical_compound quartz crystal microbalance PBS phosphate buffered saline LDL low-density lipoprotein glycosaminoglycan CSPG4 chondroitin sulfate proteoglycan 4 Macrophage Humans Heparanase Molecular Biology Cells Cultured chondroitin sulfate LC-MS2 liquid chromatography–tandem mass spectrometry proteoglycan 030102 biochemistry & molecular biology biology Macrophages Cell Biology Heparan sulfate Atherosclerosis Cell biology carbohydrates (lipids) perlecan HIF hypoxia-inducible factor Lipoproteins LDL 030104 developmental biology chemistry Proteoglycan low-density lipoprotein Low-density lipoprotein biology.protein LPS lipopolysaccharide heparan sulfate Heparitin Sulfate Heparan Sulfate Proteoglycans Research Article |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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