{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:05:47Z","timestamp":1790795147792,"version":"4.1.0"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>The E3 ubiquitin ligase inducible degrader of the low-density lipoprotein receptor (IDOL) triggers lysosomal degradation of the low-density lipoprotein receptor. The tissue-specific effects of the IDOL pathway on plasma cholesterol and atherosclerosis have not been examined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>Given that the liver is the primary determinant of plasma cholesterol levels, we sought to examine the consequence of effect of chronic liver-specific expression of a dominant-active form of IDOL in mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>We expressed a degradation-resistant, dominant-active form of IDOL (super IDOL [sIDOL]) in C57Bl\/6J mice from the liver-specific albumin promoter (L-sIDOL transgenics). L-sIDOL mice were fed a Western diet for 20 or 30 weeks and then analyzed for plasma lipid levels and atherosclerotic lesion formation. L-sIDOL mice showed dramatic reductions in hepatic low-density lipoprotein receptor protein and increased plasma low-density lipoprotein cholesterol levels on both chow and Western diets. Moreover, L-sIDOL mice developed marked atherosclerotic lesions when fed a Western diet. Lesion formation in L-sIDOL mice was more robust than in apolipoprotein E*3 Leiden mice and did not require the addition of cholate to the diet. Western diet\u2013fed L-sIDOL mice had elevated expression of liver X receptor target genes and proinflammatory genes in their aortas.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>Liver-specific expression of dominant-active IDOL is associated with hypercholesterolemia and a marked elevation in atherosclerotic lesions. Our results show that increased activity of the IDOL pathway in the liver can override other low-density lipoprotein receptor regulatory pathways leading to cardiovascular disease. L-sIDOL mice are a robust, dominantly inherited, diet-inducible model for the study of atherosclerosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.115.304440","type":"journal-article","created":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T04:40:28Z","timestamp":1402980028000},"page":"442-449","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Transgenic Expression of Dominant-Active IDOL in Liver Causes Diet-Induced Hypercholesterolemia and Atherosclerosis in Mice"],"prefix":"10.1161","volume":"115","author":[{"given":"Anna C.","family":"Calkin","sequence":"first","affiliation":[{"name":"From the Departments of Pathology and Laboratory Medicine (A.C.C., S.D.L., X.-H.W., C.H., P.T.), Department of Medicine, Division of Endocrinology (J.K., C.M.W.V.S., R.I.T.), Department of Medicine, Division of Cardiology (X.-H.W., A.J.L.), and Departments of Human Genetics and Microbiology Immunology and Molecular Genetics (A.J.L.), David Geffen School of Medicine, University of California, Los Angeles; Howard Hughes Medical Institute, Los Angeles, CA (A.C.C., S.D.L., C.H., P.T.); and Baker IDI..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Laboratory Medicine (A.C.C., S.D.L., X.-H.W., C.H., P.T.), Department of Medicine, Division of Endocrinology (J.K., C.M.W.V.S., R.I.T.), Department of Medicine, Division of Cardiology (X.-H.W., A.J.L.), and Departments of Human Genetics and Microbiology Immunology and Molecular Genetics (A.J.L.), David Geffen School of Medicine, University of California, Los Angeles; Howard Hughes Medical Institute, Los Angeles, CA (A.C.C., S.D.L., C.H., P.T.); and Baker IDI..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Laboratory Medicine (A.C.C., S.D.L., X.-H.W., C.H., P.T.), Department of Medicine, Division of Endocrinology (J.K., C.M.W.V.S., R.I.T.), Department of Medicine, Division of Cardiology (X.-H.W., A.J.L.), and Departments of Human Genetics and Microbiology Immunology and Molecular Genetics (A.J.L.), David Geffen School of Medicine, University of California, Los Angeles; Howard Hughes Medical Institute, Los Angeles, CA (A.C.C., S.D.L., C.H., P.T.); and Baker IDI..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.W.","family":"Van Stijn","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Laboratory Medicine (A.C.C., S.D.L., X.-H.W., C.H., P.T.), Department of Medicine, Division of Endocrinology (J.K., C.M.W.V.S., R.I.T.), Department of Medicine, Division of Cardiology (X.-H.W., A.J.L.), and Departments of Human Genetics and Microbiology Immunology and Molecular Genetics (A.J.L.), David Geffen School of Medicine, University of California, Los Angeles; Howard Hughes Medical Institute, Los Angeles, CA (A.C.C., S.D.L., C.H., P.T.); and Baker IDI..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hui","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Laboratory Medicine (A.C.C., S.D.L., X.-H.W., C.H., P.T.), Department of Medicine, Division of Endocrinology (J.K., C.M.W.V.S., R.I.T.), Department of Medicine, Division of Cardiology (X.-H.W., A.J.L.), and Departments of Human Genetics and Microbiology Immunology and Molecular Genetics (A.J.L.), David Geffen School of Medicine, University of California, Los Angeles; Howard Hughes Medical Institute, Los Angeles, CA (A.C.C., S.D.L., C.H., P.T.); and Baker IDI..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldons J.","family":"Lusis","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Laboratory Medicine (A.C.C., S.D.L., X.-H.W., C.H., P.T.), Department of Medicine, Division of Endocrinology (J.K., C.M.W.V.S., R.I.T.), Department of Medicine, Division of Cardiology (X.-H.W., A.J.L.), and Departments of Human Genetics and Microbiology Immunology and Molecular Genetics (A.J.L.), David Geffen School of Medicine, University of California, Los Angeles; Howard Hughes Medical Institute, Los Angeles, CA (A.C.C., S.D.L., C.H., P.T.); and Baker IDI..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Hong","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Laboratory Medicine (A.C.C., S.D.L., X.-H.W., C.H., P.T.), Department of Medicine, Division of Endocrinology (J.K., C.M.W.V.S., R.I.T.), Department of Medicine, Division of Cardiology (X.-H.W., A.J.L.), and Departments of Human Genetics and Microbiology Immunology and Molecular Genetics (A.J.L.), David Geffen School of Medicine, University of California, Los Angeles; Howard Hughes Medical Institute, Los Angeles, CA (A.C.C., S.D.L., C.H., P.T.); and Baker IDI..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra I.","family":"Tangirala","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Laboratory Medicine (A.C.C., S.D.L., X.-H.W., C.H., P.T.), Department of Medicine, Division of Endocrinology (J.K., C.M.W.V.S., R.I.T.), Department of Medicine, Division of Cardiology (X.-H.W., A.J.L.), and Departments of Human Genetics and Microbiology Immunology and Molecular Genetics (A.J.L.), David Geffen School of Medicine, University of California, Los Angeles; Howard Hughes Medical Institute, Los Angeles, CA (A.C.C., S.D.L., C.H., P.T.); and Baker IDI..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Tontonoz","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Laboratory Medicine (A.C.C., S.D.L., X.-H.W., C.H., P.T.), Department of Medicine, Division of Endocrinology (J.K., C.M.W.V.S., R.I.T.), Department of Medicine, Division of Cardiology (X.-H.W., A.J.L.), and Departments of Human Genetics and Microbiology Immunology and Molecular Genetics (A.J.L.), David Geffen School of Medicine, University of California, Los Angeles; Howard Hughes Medical Institute, Los Angeles, CA (A.C.C., S.D.L., C.H., P.T.); and Baker IDI..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168974"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111589108"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01469-10"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000730"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45504"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs472"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3513311"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118532"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(85)90138-8"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.112.300263"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117179"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117915"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1411543"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000243925.65265.3c"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.107.142570"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2009.11.043"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.115.304440","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:51:21Z","timestamp":1715572281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.115.304440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8]]},"references-count":16,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["10.1161\/CIRCRESAHA.115.304440"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.115.304440","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8]]},"assertion":[{"value":"2014-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}