{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:56:03Z","timestamp":1780466163941,"version":"3.54.1"},"reference-count":12,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T00:00:00Z","timestamp":1563408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31520103909"],"award-info":[{"award-number":["31520103909"]}],"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":["81270367"],"award-info":[{"award-number":["81270367"]}],"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":["81570787"],"award-info":[{"award-number":["81570787"]}],"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":["81770449"],"award-info":[{"award-number":["81770449"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFE0126000"],"award-info":[{"award-number":["2016YFE0126000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Objective: Familial hypercholesterolemia (FH) is a dominant inherited disease caused mainly by low-density lipoprotein receptor (LDLR) gene mutations. To different extents, both heterozygous and homozygous FH patients develop premature coronary heart disease (CHD). However, most of the experimental animal models with LDLR deficiency could not fully recapitulate FH because they develop hyperlipidemia and atherosclerosis only in homozygous, but not in heterozygous, form. In the current study, we investigated the responsiveness of the LDLR+\/\u2212 hamster to dietary cholesterol and whether plasma cholesterol levels were positively associated with the severity of atherosclerosis. Approach and Methods: wild type WT and LDLR+\/\u2212 hamsters were fed a high fat diet with different cholesterol contents (HCHF) for 12 or 16 weeks. Plasma lipids, (apo)lipoproteins, and atherosclerosis in both the aorta and coronary arteries were analyzed. After a HCHF diet challenge, the levels of total cholesterol (TC) in WT and LDLR+\/\u2212 hamsters were significantly elevated, but the latter showed a more pronounced lipoprotein profile, with higher cholesterol levels that were positively correlated with dietary cholesterol contents. The LDLR+\/\u2212 hamsters also showed accelerated atherosclerotic lesions in the aorta and coronary arteries, whereas only mild aortic lesions were observed in WT hamsters. Conclusions: Our findings demonstrate that, unlike other rodent animals, the levels of plasma cholesterol in hamsters can be significantly modulated by the intervention of dietary cholesterol, which were closely associated with severity of atherosclerosis in LDLR+\/\u2212 hamsters, suggesting that the LDLR+\/\u2212 hamster is an ideal animal model for FH and has great potential in the study of FH and atherosclerosis-related CHD.<\/jats:p>","DOI":"10.3390\/ijms20143515","type":"journal-article","created":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T03:11:42Z","timestamp":1563419502000},"page":"3515","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Dietary Cholesterol Is Highly Associated with Severity of Hyperlipidemia and Atherosclerotic Lesions in Heterozygous LDLR-Deficient Hamsters"],"prefix":"10.3390","volume":"20","author":[{"given":"Jinjie","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunxiang","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hebei Invivo Biotech Co., Shijiazhuang 050000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunde","family":"Xian","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/humu.1380010602","article-title":"Molecular genetics of the ldl receptor gene in familial hypercholesterolemia","volume":"1","author":"Hobbs","year":"1992","journal-title":"Hum. Mutat."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1093\/eurheartj\/ehu274","article-title":"Homozygous familial hypercholesterolaemia: New insights and guidance for clinicians to improve detection and clinical management. A position paper from the consensus panel on familial hypercholesterolaemia of the european atherosclerosis society","volume":"35","author":"Cuchel","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Davis, B.T., Wang, X.J., Rohret, J.A., Struzynski, J.T., Merricks, E.P., Bellinger, D.A., Rohret, F.A., Nichols, T.C., and Rogers, C.S. (2014). Targeted disruption of ldlr causes hypercholesterolemia and atherosclerosis in yucatan miniature pigs. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093457"},{"key":"ref_4","first-page":"1845","article-title":"Experimental models of murine atherosclerosis: Does perception match reality?","volume":"114","author":"Johnston","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ebiom.2017.12.013","article-title":"Ldl receptor gene-ablated hamsters: A rodent model of familial hypercholesterolemia with dominant inheritance and diet-induced coronary atherosclerosis","volume":"27","author":"Guo","year":"2018","journal-title":"Ebiomedicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1093\/femsre\/fuz008","article-title":"Drug development against human adenoviruses and its advancement by syrian hamster models","volume":"43","author":"Wold","year":"2019","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1194\/jlr.M043646","article-title":"Cholesteryl ester transfer proteins from different species do not have equivalent activities","volume":"55","author":"Morton","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_8","unstructured":"Feingold, K.R., Anawalt, B., Boyce, A., Chrousos, G., Dungan, K., Grossman, A., Hershman, J.M., Kaltsas, G., Koch, C., and Kopp, P. (2000). Introduction to lipids and lipoproteins. Endotext, MDText.com, Inc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1172\/JCI116663","article-title":"Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery","volume":"92","author":"Ishibashi","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.cmet.2016.11.001","article-title":"Applications and limitations of mouse models for understanding human atherosclerosis","volume":"25","author":"Zhao","year":"2017","journal-title":"Cell Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e131","DOI":"10.1161\/ATV.0000000000000062","article-title":"Recommendation on design, execution, and reporting of animal atherosclerosis studies: A scientific statement from the american heart association","volume":"37","author":"Daugherty","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/1743-7075-7-89","article-title":"Use of hamster as a model to study diet-induced atherosclerosis","volume":"7","author":"Dillard","year":"2010","journal-title":"Nutr. Metab."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/14\/3515\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:06:48Z","timestamp":1760188008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/14\/3515"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,18]]},"references-count":12,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["ijms20143515"],"URL":"https:\/\/doi.org\/10.3390\/ijms20143515","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,18]]}}}