{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:47:11Z","timestamp":1791287231589,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":143,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2021206399"],"award-info":[{"award-number":["H2021206399"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2019206715"],"award-info":[{"award-number":["H2019206715"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070460"],"award-info":[{"award-number":["82070460"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31771306"],"award-info":[{"award-number":["31771306"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700386"],"award-info":[{"award-number":["81700386"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Inducible degrader of low\u2010density lipoprotein (LDL) receptor (Idol) is an E3 ubiquitin ligase coded by <jats:italic>Idol<\/jats:italic>, the target gene of liver X receptor (LXR), which primarily mediates the ubiquitination and lysosomal degradation of low\u2010density lipoprotein receptor (LDLR). Previous studies from independent groups have shown that plasma cholesterol regulation by the LXR\u2010Idol\u2010LDLR axis is tissue\u2010 and species\u2010specific, indicating that the precise molecular mechanism by which Idol modulates lipid metabolism has not been completely understood and needs to be further validated in other species. Hamster, a small rodent animal model expressing endogenous cholesterol ester transfer protein (CETP), possesses many metabolic characteristics that are different from mouse but similar to human. In this study, an Idol knockout (Idol<jats:sup>-\/-<\/jats:sup>) hamster model was developed using CRISPR\/Cas9 gene editing system to investigate the effect of Idol depletion on plasma lipid metabolism and atherosclerosis. Our results showed that there were no significant differences in hepatic LDLR protein and plasma cholesterol levels in Idol<jats:sup>-\/-<\/jats:sup> hamsters compared with wild\u2010type (WT) controls, which was consistent with the observation that LXR agonist treatment increased the expression of <jats:italic>Idol<\/jats:italic> mRNA in the small intestine but not in the liver of WT hamsters. However, we found that plasma triglyceride (TG) levels were significantly reduced in Idol<jats:sup>-\/-<\/jats:sup> hamsters due to an enhancement of TG clearance. In addition, the morphological data demonstrated that inactivation of Idol significantly lowered plasma total cholesterol and TG levels and protected against spontaneous atherosclerotic lesions in aged LDLR knockout hamsters on a chow diet but had no effect on diet\u2010induced atherosclerosis in hamsters lacking one copy of the <jats:italic>Ldlr<\/jats:italic> gene. In conclusion, our findings suggest that Idol can regulate plasma lipid metabolism and atherosclerosis independent of LDLR function.<\/jats:p>","DOI":"10.1155\/2022\/1889632","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T17:06:23Z","timestamp":1653411983000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Idol Depletion Protects against Spontaneous Atherosclerosis in a Hamster Model of Familial Hypercholesterolemia"],"prefix":"10.1155","volume":"2022","author":[{"given":"Chenxi","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3059-1254","authenticated-orcid":false,"given":"Xunde","family":"Xian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0589-7633","authenticated-orcid":false,"given":"Mingming","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3513311"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800054-JLR200"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409736102"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-018-0107-8"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168974"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2056211"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01716-12"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45504"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000089"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs472"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312589"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.10.001"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.304440"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw010"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.12.013"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2020.154296"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2018.03.003"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1139\/y59-099"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.306032"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M016410"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0300-9629(91)90263-C"},{"key":"e_1_2_9_22_2","first-page":"1","article-title":"Experimental obstructive coronary atherosclerosis in the hyperlipidemic hamster","volume":"22","author":"Sima A.","year":"1990","journal-title":"Journal of Submicroscopic Cytology and Pathology"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21514"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.38.26761"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6875-6_6"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.044795"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/1889632.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/1889632.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2022\/1889632","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T23:59:13Z","timestamp":1748908753000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2022\/1889632"}},"subtitle":[],"editor":[{"given":"Ramoji","family":"Kosuru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1155\/2022\/1889632"],"URL":"https:\/\/doi.org\/10.1155\/2022\/1889632","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"2022-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1889632"}}