T-0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor-deficient mice
Liver X receptors (LXRα and LXRβ) are nuclear receptors, which are important regulators of cholesterol and lipid metabolism. LXRs control genes involved in cholesterol efflux in macrophages, bile acid synthesis in liver and intestinal cholesterol absorption. LXRs also regulate genes participating in...
Gespeichert in:
| Veröffentlicht in: | FEBS letters 2003-02, Vol.536 (1), p.6-11 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 11 |
|---|---|
| container_issue | 1 |
| container_start_page | 6 |
| container_title | FEBS letters |
| container_volume | 536 |
| creator | Terasaka, Naoki Hiroshima, Ayano Koieyama, Tadashi Ubukata, Naoko Morikawa, Yuka Nakai, Daisuke Inaba, Toshimori |
| description | Liver X receptors (LXRα and LXRβ) are nuclear receptors, which are important regulators of cholesterol and lipid metabolism. LXRs control genes involved in cholesterol efflux in macrophages, bile acid synthesis in liver and intestinal cholesterol absorption. LXRs also regulate genes participating in lipogenesis. To determine whether the activation of LXR promotes or inhibits development of atherosclerosis, T-0901317, a synthetic LXR ligand, was administered to low density lipoprotein receptor (LDLR)
−/− mice. T-0901317 significantly reduced the atherosclerotic lesions in LDLR
−/− mice without affecting plasma total cholesterol levels. This anti-atherogenic effect correlated with the plasma concentration of T-0901317, but not with high density lipoprotein cholesterol, which was increased by T-0901317. In addition, we observed that T-0901317 increased expression of ATP binding cassette A1 in the lesions in LDLR
−/− mice as well as in mouse peritoneal macrophages. T-0901317 also significantly induced cholesterol efflux activity in peritoneal macrophages. These results suggest that LXR ligands may be useful therapeutic agents for the treatment of atherosclerosis. |
| doi_str_mv | 10.1016/S0014-5793(02)03578-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_73024137</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0014579302035780</els_id><sourcerecordid>73024137</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5090-565e460fb02bb097943cf279f13880b7dbf37daf9451729be45f68b8b68991733</originalsourceid><addsrcrecordid>eNqNkctuEzEUhi1ERUPgEUBeIZA6cGyPx_YKQelNisSCIrGzxp5jajSXdDwJytvjSaKybDe2fM53Lv5_Qt4w-MiAVZ9-ALCykMqI98A_gJBKF_CMLJhWohBlpZ-TxQNySl6m9AfyWzPzgpwyLnUluFmQ7W0BBphg6ozWNO366Q6n6GkbtzjSX3REj-tpGHPgd903ZzT2d9HFKdEGt9gO6w77iQ6B1rlwHJJv5zOmzNHVt9VDfdFgiD7OcBc9viInoW4Tvj7eS_Lz8uL2_LpYfb-6Of-yKrzMaxWyklhWEBxw58AoUwofuDKBCa3BqcYFoZo6mFIyxY3DUoZKO-0qbQxTQizJu0Pf9TjcbzBNtovJY9vWPQ6bZJUAXjKhHgWZ4SxLVmVQHkCf_5lGDHY9xq4ed5aBnZ2xe2fsLLsFbvfO5HNJ3h4HbFyHzf-qoxUZuD4Af2OLu6d1tZcXX_k-MyeA78PzrM-HVpil3UYcbZql99jE7MdkmyE-su0_HTSwGA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>19218636</pqid></control><display><type>article</type><title>T-0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor-deficient mice</title><source>Wiley Free Content</source><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elsevier ScienceDirect Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Terasaka, Naoki ; Hiroshima, Ayano ; Koieyama, Tadashi ; Ubukata, Naoko ; Morikawa, Yuka ; Nakai, Daisuke ; Inaba, Toshimori</creator><creatorcontrib>Terasaka, Naoki ; Hiroshima, Ayano ; Koieyama, Tadashi ; Ubukata, Naoko ; Morikawa, Yuka ; Nakai, Daisuke ; Inaba, Toshimori</creatorcontrib><description>Liver X receptors (LXRα and LXRβ) are nuclear receptors, which are important regulators of cholesterol and lipid metabolism. LXRs control genes involved in cholesterol efflux in macrophages, bile acid synthesis in liver and intestinal cholesterol absorption. LXRs also regulate genes participating in lipogenesis. To determine whether the activation of LXR promotes or inhibits development of atherosclerosis, T-0901317, a synthetic LXR ligand, was administered to low density lipoprotein receptor (LDLR)
−/− mice. T-0901317 significantly reduced the atherosclerotic lesions in LDLR
−/− mice without affecting plasma total cholesterol levels. This anti-atherogenic effect correlated with the plasma concentration of T-0901317, but not with high density lipoprotein cholesterol, which was increased by T-0901317. In addition, we observed that T-0901317 increased expression of ATP binding cassette A1 in the lesions in LDLR
−/− mice as well as in mouse peritoneal macrophages. T-0901317 also significantly induced cholesterol efflux activity in peritoneal macrophages. These results suggest that LXR ligands may be useful therapeutic agents for the treatment of atherosclerosis.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/S0014-5793(02)03578-0</identifier><identifier>PMID: 12586329</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>ABC, ATP binding cassette ; Animals ; Anticholesteremic Agents - therapeutic use ; apoA-I, apolipoprotein A-I ; Arteriosclerosis - metabolism ; Arteriosclerosis - pathology ; Arteriosclerosis - prevention & control ; Atherosclerosis ; ATP binding cassette A1 ; ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters - biosynthesis ; ATP-Binding Cassette Transporters - genetics ; Biological Transport ; Cholesterol - metabolism ; Cholesterol efflux ; DNA-Binding Proteins ; FAS, fatty acid synthetase ; HDL, high density lipoprotein ; HPLC, high performance liquid chromatography ; Hydrocarbons, Fluorinated ; LDL, low density lipoprotein ; Ligands ; Lipids - blood ; Lipoproteins - blood ; Liver X receptor ; Liver X Receptors ; LXR, liver X receptor ; Macrophage ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Biological ; Nuclear receptor ; Orphan Nuclear Receptors ; Receptors, Cytoplasmic and Nuclear - agonists ; Receptors, LDL - genetics ; RNA, Messenger - biosynthesis ; SCD-1, stearoyl CoA desaturase 1 ; SREBP-1c, sterol response element binding protein 1c ; Sulfonamides ; TC, total cholesterol ; TG, triglycerides ; VLDL, very low density lipoprotein</subject><ispartof>FEBS letters, 2003-02, Vol.536 (1), p.6-11</ispartof><rights>2002 Federation of European Biochemical Societies</rights><rights>FEBS Letters 536 (2003) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5090-565e460fb02bb097943cf279f13880b7dbf37daf9451729be45f68b8b68991733</citedby><cites>FETCH-LOGICAL-c5090-565e460fb02bb097943cf279f13880b7dbf37daf9451729be45f68b8b68991733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2FS0014-5793%2802%2903578-0$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014579302035780$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,1427,3537,27901,27902,45550,45551,46384,46808,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12586329$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Terasaka, Naoki</creatorcontrib><creatorcontrib>Hiroshima, Ayano</creatorcontrib><creatorcontrib>Koieyama, Tadashi</creatorcontrib><creatorcontrib>Ubukata, Naoko</creatorcontrib><creatorcontrib>Morikawa, Yuka</creatorcontrib><creatorcontrib>Nakai, Daisuke</creatorcontrib><creatorcontrib>Inaba, Toshimori</creatorcontrib><title>T-0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor-deficient mice</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>Liver X receptors (LXRα and LXRβ) are nuclear receptors, which are important regulators of cholesterol and lipid metabolism. LXRs control genes involved in cholesterol efflux in macrophages, bile acid synthesis in liver and intestinal cholesterol absorption. LXRs also regulate genes participating in lipogenesis. To determine whether the activation of LXR promotes or inhibits development of atherosclerosis, T-0901317, a synthetic LXR ligand, was administered to low density lipoprotein receptor (LDLR)
−/− mice. T-0901317 significantly reduced the atherosclerotic lesions in LDLR
−/− mice without affecting plasma total cholesterol levels. This anti-atherogenic effect correlated with the plasma concentration of T-0901317, but not with high density lipoprotein cholesterol, which was increased by T-0901317. In addition, we observed that T-0901317 increased expression of ATP binding cassette A1 in the lesions in LDLR
−/− mice as well as in mouse peritoneal macrophages. T-0901317 also significantly induced cholesterol efflux activity in peritoneal macrophages. These results suggest that LXR ligands may be useful therapeutic agents for the treatment of atherosclerosis.</description><subject>ABC, ATP binding cassette</subject><subject>Animals</subject><subject>Anticholesteremic Agents - therapeutic use</subject><subject>apoA-I, apolipoprotein A-I</subject><subject>Arteriosclerosis - metabolism</subject><subject>Arteriosclerosis - pathology</subject><subject>Arteriosclerosis - prevention & control</subject><subject>Atherosclerosis</subject><subject>ATP binding cassette A1</subject><subject>ATP Binding Cassette Transporter 1</subject><subject>ATP-Binding Cassette Transporters - biosynthesis</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>Biological Transport</subject><subject>Cholesterol - metabolism</subject><subject>Cholesterol efflux</subject><subject>DNA-Binding Proteins</subject><subject>FAS, fatty acid synthetase</subject><subject>HDL, high density lipoprotein</subject><subject>HPLC, high performance liquid chromatography</subject><subject>Hydrocarbons, Fluorinated</subject><subject>LDL, low density lipoprotein</subject><subject>Ligands</subject><subject>Lipids - blood</subject><subject>Lipoproteins - blood</subject><subject>Liver X receptor</subject><subject>Liver X Receptors</subject><subject>LXR, liver X receptor</subject><subject>Macrophage</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Models, Biological</subject><subject>Nuclear receptor</subject><subject>Orphan Nuclear Receptors</subject><subject>Receptors, Cytoplasmic and Nuclear - agonists</subject><subject>Receptors, LDL - genetics</subject><subject>RNA, Messenger - biosynthesis</subject><subject>SCD-1, stearoyl CoA desaturase 1</subject><subject>SREBP-1c, sterol response element binding protein 1c</subject><subject>Sulfonamides</subject><subject>TC, total cholesterol</subject><subject>TG, triglycerides</subject><subject>VLDL, very low density lipoprotein</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkctuEzEUhi1ERUPgEUBeIZA6cGyPx_YKQelNisSCIrGzxp5jajSXdDwJytvjSaKybDe2fM53Lv5_Qt4w-MiAVZ9-ALCykMqI98A_gJBKF_CMLJhWohBlpZ-TxQNySl6m9AfyWzPzgpwyLnUluFmQ7W0BBphg6ozWNO366Q6n6GkbtzjSX3REj-tpGHPgd903ZzT2d9HFKdEGt9gO6w77iQ6B1rlwHJJv5zOmzNHVt9VDfdFgiD7OcBc9viInoW4Tvj7eS_Lz8uL2_LpYfb-6Of-yKrzMaxWyklhWEBxw58AoUwofuDKBCa3BqcYFoZo6mFIyxY3DUoZKO-0qbQxTQizJu0Pf9TjcbzBNtovJY9vWPQ6bZJUAXjKhHgWZ4SxLVmVQHkCf_5lGDHY9xq4ed5aBnZ2xe2fsLLsFbvfO5HNJ3h4HbFyHzf-qoxUZuD4Af2OLu6d1tZcXX_k-MyeA78PzrM-HVpil3UYcbZql99jE7MdkmyE-su0_HTSwGA</recordid><startdate>20030211</startdate><enddate>20030211</enddate><creator>Terasaka, Naoki</creator><creator>Hiroshima, Ayano</creator><creator>Koieyama, Tadashi</creator><creator>Ubukata, Naoko</creator><creator>Morikawa, Yuka</creator><creator>Nakai, Daisuke</creator><creator>Inaba, Toshimori</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20030211</creationdate><title>T-0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor-deficient mice</title><author>Terasaka, Naoki ; Hiroshima, Ayano ; Koieyama, Tadashi ; Ubukata, Naoko ; Morikawa, Yuka ; Nakai, Daisuke ; Inaba, Toshimori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5090-565e460fb02bb097943cf279f13880b7dbf37daf9451729be45f68b8b68991733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>ABC, ATP binding cassette</topic><topic>Animals</topic><topic>Anticholesteremic Agents - therapeutic use</topic><topic>apoA-I, apolipoprotein A-I</topic><topic>Arteriosclerosis - metabolism</topic><topic>Arteriosclerosis - pathology</topic><topic>Arteriosclerosis - prevention & control</topic><topic>Atherosclerosis</topic><topic>ATP binding cassette A1</topic><topic>ATP Binding Cassette Transporter 1</topic><topic>ATP-Binding Cassette Transporters - biosynthesis</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>Biological Transport</topic><topic>Cholesterol - metabolism</topic><topic>Cholesterol efflux</topic><topic>DNA-Binding Proteins</topic><topic>FAS, fatty acid synthetase</topic><topic>HDL, high density lipoprotein</topic><topic>HPLC, high performance liquid chromatography</topic><topic>Hydrocarbons, Fluorinated</topic><topic>LDL, low density lipoprotein</topic><topic>Ligands</topic><topic>Lipids - blood</topic><topic>Lipoproteins - blood</topic><topic>Liver X receptor</topic><topic>Liver X Receptors</topic><topic>LXR, liver X receptor</topic><topic>Macrophage</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Models, Biological</topic><topic>Nuclear receptor</topic><topic>Orphan Nuclear Receptors</topic><topic>Receptors, Cytoplasmic and Nuclear - agonists</topic><topic>Receptors, LDL - genetics</topic><topic>RNA, Messenger - biosynthesis</topic><topic>SCD-1, stearoyl CoA desaturase 1</topic><topic>SREBP-1c, sterol response element binding protein 1c</topic><topic>Sulfonamides</topic><topic>TC, total cholesterol</topic><topic>TG, triglycerides</topic><topic>VLDL, very low density lipoprotein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Terasaka, Naoki</creatorcontrib><creatorcontrib>Hiroshima, Ayano</creatorcontrib><creatorcontrib>Koieyama, Tadashi</creatorcontrib><creatorcontrib>Ubukata, Naoko</creatorcontrib><creatorcontrib>Morikawa, Yuka</creatorcontrib><creatorcontrib>Nakai, Daisuke</creatorcontrib><creatorcontrib>Inaba, Toshimori</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Terasaka, Naoki</au><au>Hiroshima, Ayano</au><au>Koieyama, Tadashi</au><au>Ubukata, Naoko</au><au>Morikawa, Yuka</au><au>Nakai, Daisuke</au><au>Inaba, Toshimori</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>T-0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor-deficient mice</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>2003-02-11</date><risdate>2003</risdate><volume>536</volume><issue>1</issue><spage>6</spage><epage>11</epage><pages>6-11</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>Liver X receptors (LXRα and LXRβ) are nuclear receptors, which are important regulators of cholesterol and lipid metabolism. LXRs control genes involved in cholesterol efflux in macrophages, bile acid synthesis in liver and intestinal cholesterol absorption. LXRs also regulate genes participating in lipogenesis. To determine whether the activation of LXR promotes or inhibits development of atherosclerosis, T-0901317, a synthetic LXR ligand, was administered to low density lipoprotein receptor (LDLR)
−/− mice. T-0901317 significantly reduced the atherosclerotic lesions in LDLR
−/− mice without affecting plasma total cholesterol levels. This anti-atherogenic effect correlated with the plasma concentration of T-0901317, but not with high density lipoprotein cholesterol, which was increased by T-0901317. In addition, we observed that T-0901317 increased expression of ATP binding cassette A1 in the lesions in LDLR
−/− mice as well as in mouse peritoneal macrophages. T-0901317 also significantly induced cholesterol efflux activity in peritoneal macrophages. These results suggest that LXR ligands may be useful therapeutic agents for the treatment of atherosclerosis.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>12586329</pmid><doi>10.1016/S0014-5793(02)03578-0</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-5793 |
| ispartof | FEBS letters, 2003-02, Vol.536 (1), p.6-11 |
| issn | 0014-5793 1873-3468 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_73024137 |
| source | Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | ABC, ATP binding cassette Animals Anticholesteremic Agents - therapeutic use apoA-I, apolipoprotein A-I Arteriosclerosis - metabolism Arteriosclerosis - pathology Arteriosclerosis - prevention & control Atherosclerosis ATP binding cassette A1 ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters - biosynthesis ATP-Binding Cassette Transporters - genetics Biological Transport Cholesterol - metabolism Cholesterol efflux DNA-Binding Proteins FAS, fatty acid synthetase HDL, high density lipoprotein HPLC, high performance liquid chromatography Hydrocarbons, Fluorinated LDL, low density lipoprotein Ligands Lipids - blood Lipoproteins - blood Liver X receptor Liver X Receptors LXR, liver X receptor Macrophage Male Mice Mice, Inbred C57BL Mice, Knockout Models, Biological Nuclear receptor Orphan Nuclear Receptors Receptors, Cytoplasmic and Nuclear - agonists Receptors, LDL - genetics RNA, Messenger - biosynthesis SCD-1, stearoyl CoA desaturase 1 SREBP-1c, sterol response element binding protein 1c Sulfonamides TC, total cholesterol TG, triglycerides VLDL, very low density lipoprotein |
| title | T-0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor-deficient mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T07%3A39%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=T-0901317,%20a%20synthetic%20liver%20X%20receptor%20ligand,%20inhibits%20development%20of%20atherosclerosis%20in%20LDL%20receptor-deficient%20mice&rft.jtitle=FEBS%20letters&rft.au=Terasaka,%20Naoki&rft.date=2003-02-11&rft.volume=536&rft.issue=1&rft.spage=6&rft.epage=11&rft.pages=6-11&rft.issn=0014-5793&rft.eissn=1873-3468&rft_id=info:doi/10.1016/S0014-5793(02)03578-0&rft_dat=%3Cproquest_cross%3E73024137%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=19218636&rft_id=info:pmid/12586329&rft_els_id=S0014579302035780&rfr_iscdi=true |