{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:32:36Z","timestamp":1791329556055,"version":"4.3.1"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2006,1,3]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Liver X receptors (LXRs) are ligand-activated transcription factors involved in the control of lipid metabolism and inflammation. Synthetic LXR agonists have been shown to inhibit the progression of atherosclerosis in mice, but the mechanism is uncertain. LXR agonism upregulates the genes encoding ATP binding cassette transporters A1 (ABCA1) and G1 (ABCG1) in macrophages, thus promoting efflux of cholesterol; it also upregulates liver and intestinal ABCG5 and ABCG8, helping to promote biliary and fecal excretion of cholesterol. Thus, LXR agonism may inhibit atherosclerosis through promotion of reverse cholesterol transport (RCT) in vivo, but this has not been proven. We previously described an in vivo method to trace the movement of cholesterol from\n            <jats:sup>3<\/jats:sup>\n            H-cholesterol\u2013labeled J774 macrophages into plasma, into liver, and ultimately into the bile and feces as free cholesterol or bile acids. In the present study we used this approach to test the hypothesis that administration of the synthetic LXR agonist GW3965 would increase the rate of macrophage RCT in vivo.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Three different mouse models\u2014wild-type C57BL\/6 mice, LDLR\/apobec-1 double knockout mice, and human apolipoprotein (apo)B\/cholesteryl ester transfer protein (CETP) double transgenic mice\u2014were treated with either vehicle or GW3965. Mice were injected intraperitoneally with\n            <jats:sup>3<\/jats:sup>\n            H-cholesterol\u2013labeled and cholesterol-loaded macrophages and monitored for the appearance of\n            <jats:sup>3<\/jats:sup>\n            H-tracer in plasma, liver, and feces. Administration of GW3965 significantly increased the levels of\n            <jats:sup>3<\/jats:sup>\n            H-tracer in plasma and feces in all 3 mouse models.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            These results demonstrate that administration of the LXR agonist GW3965 increases the rate of RCT from macrophages to feces in vivo.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.105.560177","type":"journal-article","created":{"date-parts":[[2005,12,20]],"date-time":"2005-12-20T01:34:52Z","timestamp":1135042492000},"page":"90-97","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":327,"title":["Pharmacological Activation of Liver X Receptors Promotes Reverse Cholesterol Transport In Vivo"],"prefix":"10.1161","volume":"113","author":[{"given":"Snehal U.","family":"Naik","sequence":"first","affiliation":[{"name":"From the Institute for Translational Medicine and Therapeutics (S.U.N., X.W., M.P.R., J.T.B., D.J.R.), Cardiovascular Institute (M.P.R., D.J.R.), and Institute for Diabetes Obesity and Metabolism (M.P.R., D.J.R.), University of Pennsylvania School of Medicine, Philadelphia; The Children\u2019s Hospital of Philadelphia, Philadelphia, Pa (J.S.D., G.H.R.); and GlaxoSmithKline, King of Prussia, Pa (M.J., C.H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Institute for Translational Medicine and Therapeutics (S.U.N., X.W., M.P.R., J.T.B., D.J.R.), Cardiovascular Institute (M.P.R., D.J.R.), and Institute for Diabetes Obesity and Metabolism (M.P.R., D.J.R.), University of Pennsylvania School of Medicine, Philadelphia; The Children\u2019s Hospital of Philadelphia, Philadelphia, Pa (J.S.D., G.H.R.); and GlaxoSmithKline, King of Prussia, Pa (M.J., C.H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaqueline S.","family":"Da Silva","sequence":"additional","affiliation":[{"name":"From the Institute for Translational Medicine and Therapeutics (S.U.N., X.W., M.P.R., J.T.B., D.J.R.), Cardiovascular Institute (M.P.R., D.J.R.), and Institute for Diabetes Obesity and Metabolism (M.P.R., D.J.R.), University of Pennsylvania School of Medicine, Philadelphia; The Children\u2019s Hospital of Philadelphia, Philadelphia, Pa (J.S.D., G.H.R.); and GlaxoSmithKline, King of Prussia, Pa (M.J., C.H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Jaye","sequence":"additional","affiliation":[{"name":"From the Institute for Translational Medicine and Therapeutics (S.U.N., X.W., M.P.R., J.T.B., D.J.R.), Cardiovascular Institute (M.P.R., D.J.R.), and Institute for Diabetes Obesity and Metabolism (M.P.R., D.J.R.), University of Pennsylvania School of Medicine, Philadelphia; The Children\u2019s Hospital of Philadelphia, Philadelphia, Pa (J.S.D., G.H.R.); and GlaxoSmithKline, King of Prussia, Pa (M.J., C.H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin H.","family":"Macphee","sequence":"additional","affiliation":[{"name":"From the Institute for Translational Medicine and Therapeutics (S.U.N., X.W., M.P.R., J.T.B., D.J.R.), Cardiovascular Institute (M.P.R., D.J.R.), and Institute for Diabetes Obesity and Metabolism (M.P.R., D.J.R.), University of Pennsylvania School of Medicine, Philadelphia; The Children\u2019s Hospital of Philadelphia, Philadelphia, Pa (J.S.D., G.H.R.); and GlaxoSmithKline, King of Prussia, Pa (M.J., C.H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muredach P.","family":"Reilly","sequence":"additional","affiliation":[{"name":"From the Institute for Translational Medicine and Therapeutics (S.U.N., X.W., M.P.R., J.T.B., D.J.R.), Cardiovascular Institute (M.P.R., D.J.R.), and Institute for Diabetes Obesity and Metabolism (M.P.R., D.J.R.), University of Pennsylvania School of Medicine, Philadelphia; The Children\u2019s Hospital of Philadelphia, Philadelphia, Pa (J.S.D., G.H.R.); and GlaxoSmithKline, King of Prussia, Pa (M.J., C.H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey T.","family":"Billheimer","sequence":"additional","affiliation":[{"name":"From the Institute for Translational Medicine and Therapeutics (S.U.N., X.W., M.P.R., J.T.B., D.J.R.), Cardiovascular Institute (M.P.R., D.J.R.), and Institute for Diabetes Obesity and Metabolism (M.P.R., D.J.R.), University of Pennsylvania School of Medicine, Philadelphia; The Children\u2019s Hospital of Philadelphia, Philadelphia, Pa (J.S.D., G.H.R.); and GlaxoSmithKline, King of Prussia, Pa (M.J., C.H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George H.","family":"Rothblat","sequence":"additional","affiliation":[{"name":"From the Institute for Translational Medicine and Therapeutics (S.U.N., X.W., M.P.R., J.T.B., D.J.R.), Cardiovascular Institute (M.P.R., D.J.R.), and Institute for Diabetes Obesity and Metabolism (M.P.R., D.J.R.), University of Pennsylvania School of Medicine, Philadelphia; The Children\u2019s Hospital of Philadelphia, Philadelphia, Pa (J.S.D., G.H.R.); and GlaxoSmithKline, King of Prussia, Pa (M.J., C.H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Rader","sequence":"additional","affiliation":[{"name":"From the Institute for Translational Medicine and Therapeutics (S.U.N., X.W., M.P.R., J.T.B., D.J.R.), Cardiovascular Institute (M.P.R., D.J.R.), and Institute for Diabetes Obesity and Metabolism (M.P.R., D.J.R.), University of Pennsylvania School of Medicine, Philadelphia; The Children\u2019s Hospital of Philadelphia, Philadelphia, Pa (J.S.D., G.H.R.); and GlaxoSmithKline, King of Prussia, Pa (M.J., C.H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0061"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5484.1524"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308420200"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.01.002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.8.4245"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9794"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.200367697"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3243"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.112059299"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.182199799"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000150044.84012.68"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R400010-JLR200"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm820"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000086981.09834.e0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0255116"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1139\/y59-099"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0898-934"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206522200"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8573"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.17.6.1045"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M300511-JLR200"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)39866-7"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109927200"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301311200"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1080\/07853890310020635"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.10.006"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1658"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M500116-JLR200"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.09.032"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.105.560177","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T04:37:00Z","timestamp":1715575020000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.105.560177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1,3]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1,3]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.105.560177"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.105.560177","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1,3]]},"assertion":[{"value":"2005-12-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}