Serum amyloid A-containing HDL binds adipocyte-derived versican and macrophage-derived biglycan, reducing its antiinflammatory properties
The ability of HDL to inhibit inflammation in adipocytes and adipose tissue is reduced when HDL contains serum amyloid A (SAA) that is trapped by proteoglycans at the adipocyte surface. Because we recently found that the major extracellular matrix proteoglycan produced by hypertrophic adipocytes is versican, whereas activated adipose tissue macrophages produce mainly biglycan, we further investigated the role of proteoglycans in determining the antiinflammatory properties of HDL. The distributions of versican, biglycan, apolipoprotein A1 (the major apolipoprotein of HDL), and SAA were similar in adipose tissue from obese mice and obese human subjects. Colocalization of SAA-enriched HDL with versican and biglycan at the cell surface of adipocyte and peritoneal macrophages, respectively, was blocked by silencing these proteoglycans, which also restored the antiinflammatory property of SAA-enriched HDL despite the presence of SAA. Similar to adipocytes, normal HDL exerted its antiinflammatory function in macrophages by reducing lipid rafts, reactive oxygen species generation, and translocation of Toll-like receptor 4 and NADPH oxidase 2 into lipid rafts, effects that were not observed with SAA-enriched HDL. These findings imply that SAA present in HDL can be trapped by adipocyte-derived versican and macrophage-derived biglycan, thereby blunting HDL's antiinflammatory properties.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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Enthalten in: |
JCI insight - 5(2020), 20 vom: 24. Sept. |
Sprache: |
Englisch |
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Beteiligte Personen: |
Han, Chang Yeop [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 19.05.2021 Date Revised 23.09.2021 published: Electronic Citation Status MEDLINE |
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doi: |
10.1172/jci.insight.142635 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM315414561 |
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100 | 1 | |a Han, Chang Yeop |e verfasserin |4 aut | |
245 | 1 | 0 | |a Serum amyloid A-containing HDL binds adipocyte-derived versican and macrophage-derived biglycan, reducing its antiinflammatory properties |
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520 | |a The ability of HDL to inhibit inflammation in adipocytes and adipose tissue is reduced when HDL contains serum amyloid A (SAA) that is trapped by proteoglycans at the adipocyte surface. Because we recently found that the major extracellular matrix proteoglycan produced by hypertrophic adipocytes is versican, whereas activated adipose tissue macrophages produce mainly biglycan, we further investigated the role of proteoglycans in determining the antiinflammatory properties of HDL. The distributions of versican, biglycan, apolipoprotein A1 (the major apolipoprotein of HDL), and SAA were similar in adipose tissue from obese mice and obese human subjects. Colocalization of SAA-enriched HDL with versican and biglycan at the cell surface of adipocyte and peritoneal macrophages, respectively, was blocked by silencing these proteoglycans, which also restored the antiinflammatory property of SAA-enriched HDL despite the presence of SAA. Similar to adipocytes, normal HDL exerted its antiinflammatory function in macrophages by reducing lipid rafts, reactive oxygen species generation, and translocation of Toll-like receptor 4 and NADPH oxidase 2 into lipid rafts, effects that were not observed with SAA-enriched HDL. These findings imply that SAA present in HDL can be trapped by adipocyte-derived versican and macrophage-derived biglycan, thereby blunting HDL's antiinflammatory properties | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Adipose tissue | |
650 | 4 | |a Cell Biology | |
650 | 4 | |a Inflammation | |
650 | 4 | |a Lipoproteins | |
650 | 4 | |a Macrophages | |
650 | 7 | |a APOA1 protein, human |2 NLM | |
650 | 7 | |a Apolipoprotein A-I |2 NLM | |
650 | 7 | |a BGN protein, human |2 NLM | |
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650 | 7 | |a Lipoproteins, HDL |2 NLM | |
650 | 7 | |a RNA, Small Interfering |2 NLM | |
650 | 7 | |a Reactive Oxygen Species |2 NLM | |
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650 | 7 | |a TLR4 protein, human |2 NLM | |
650 | 7 | |a Toll-Like Receptor 4 |2 NLM | |
650 | 7 | |a VCAN protein, human |2 NLM | |
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700 | 1 | |a Omer, Mohamed |e verfasserin |4 aut | |
700 | 1 | |a Wang, Shari |e verfasserin |4 aut | |
700 | 1 | |a Wietecha, Tomasz |e verfasserin |4 aut | |
700 | 1 | |a Wight, Thomas N |e verfasserin |4 aut | |
700 | 1 | |a Chait, Alan |e verfasserin |4 aut | |
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