{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T22:25:07Z","timestamp":1793917507225,"version":"4.8.0"},"reference-count":33,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100017700","name":"Henan Provincial Science and Technology Research Project","doi-asserted-by":"publisher","award":["LHGJ20230522"],"award-info":[{"award-number":["LHGJ20230522"]}],"id":[{"id":"10.13039\/501100017700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8227022022"],"award-info":[{"award-number":["8227022022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology and Applied Pharmacology"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.taap.2026.118047","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:09:28Z","timestamp":1790809768000},"page":"118047","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Levonorgestrel-ethinyl estradiol impairs hepatic lipid clearance to induce hypercholesterolemia via PCSK9-mediated LDLR and CD36 dysregulation"],"prefix":"10.1016","volume":"517","author":[{"given":"Bingzhi","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenji","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghui","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghua","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.taap.2026.118047_bb0005","doi-asserted-by":"crossref","first-page":"444","DOI":"10.3109\/13625187.2011.604450","article-title":"Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17\u03b2-oestradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism","volume":"16","author":"\u00c5gren","year":"2011","journal-title":"Eur J Contracept Reprod Health Care"},{"key":"10.1016\/j.taap.2026.118047_bb0010","article-title":"Hypertriglyceridemia-induced acute pancreatitis exacerbated by combined oral contraceptive use: a case report","volume":"16","author":"Bhatt","year":"2024","journal-title":"Cureus"},{"key":"10.1016\/j.taap.2026.118047_bb0015","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1007\/s00228-024-03671-z","article-title":"Oral contraceptives in adolescents: a retrospective population-based study on blood pressure and metabolic dysregulation","volume":"80","author":"de Ara\u00fajo","year":"2024","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"10.1016\/j.taap.2026.118047_bb0020","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1161\/ATVBAHA.115.306032","article-title":"PCSK9 induces CD36 degradation and affects long-chain fatty acid uptake and triglyceride metabolism in adipocytes and in mouse liver","volume":"35","author":"Demers","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.taap.2026.118047_bb0025","article-title":"Metformin versus the combined oral contraceptive pill for hirsutism, acne, and menstrual pattern in polycystic ovary syndrome","volume":"8","author":"E","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.taap.2026.118047_bb0030","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1016\/S0140-6736(24)00367-2","article-title":"Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021","volume":"403","year":"2024","journal-title":"Lancet"},{"key":"10.1016\/j.taap.2026.118047_bb0035","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1152\/physrev.00011.2023","article-title":"CD36 as a gatekeeper of myocardial lipid metabolism and therapeutic target for metabolic disease","volume":"104","author":"Glatz","year":"2024","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.taap.2026.118047_bb0040","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1161\/CIRCULATIONAHA.124.072336","article-title":"PCSK9 promotes LDLR degradation by preventing SNX17-mediated LDLR recycling","volume":"151","author":"Guan","year":"2025","journal-title":"Circulation"},{"key":"10.1016\/j.taap.2026.118047_bb0045","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.1038\/s41467-020-18565-8","article-title":"CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis","volume":"11","author":"Hao","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.taap.2026.118047_bb0050","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1186\/s12905-023-02703-7","article-title":"Association between oral contraceptives with lipid profile: results from Hoveyzeh cohort study (HCS)","volume":"23","author":"Hashemi","year":"2023","journal-title":"BMC Womens Health"},{"key":"10.1016\/j.taap.2026.118047_bb0055","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2023.108480","article-title":"Targeting PCSK9 to tackle cardiovascular disease","volume":"249","author":"Hummelgaard","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.taap.2026.118047_bb0060","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.imlet.2023.12.002","article-title":"CD36 as a double-edged sword in cancer","volume":"265","author":"Jiang","year":"2024","journal-title":"Immunol. Lett."},{"key":"10.1016\/j.taap.2026.118047_bb0065","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1161\/CIRCRESAHA.121.320056","article-title":"Proprotein convertase subtilisin\/Kexin 9 (PCSK9) promotes macrophage activation via LDL receptor-independent mechanisms","volume":"131","author":"Katsuki","year":"2022","journal-title":"Circ. Res."},{"key":"10.1016\/j.taap.2026.118047_bb0070","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.clinbiochem.2009.12.013","article-title":"Effect of second and third generation oral contraceptives on C-reactive protein, lipids and apolipoproteins in young, non-obese, non-smoking apparently healthy women","volume":"43","author":"Krintus","year":"2010","journal-title":"Clin. Biochem."},{"key":"10.1016\/j.taap.2026.118047_bb0075","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/MOL.0000000000000114","article-title":"PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells","volume":"25","author":"Lagace","year":"2014","journal-title":"Curr. Opin. Lipidol."},{"key":"10.1016\/j.taap.2026.118047_bb0080","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.taap.2026.118047_bb0085","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk","volume":"41","author":"Mach","year":"2020","journal-title":"Eur. Heart J."},{"key":"10.1016\/j.taap.2026.118047_bb0090","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1681\/ASN.2008010009","article-title":"CD36 regulates oxidative stress and inflammation in hypercholesterolemic CKD","volume":"20","author":"Okamura","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.taap.2026.118047_bb0095","first-page":"1129","article-title":"2021 Canadian cardiovascular society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in adults","volume":"37","author":"Pearson","year":"2021","journal-title":"Can. J. Cardiol."},{"key":"10.1016\/j.taap.2026.118047_bb0100","doi-asserted-by":"crossref","DOI":"10.1007\/s11883-018-0715-0","article-title":"The interplay of lipids, lipoproteins, and immunity in atherosclerosis","volume":"20","author":"Pirillo","year":"2018","journal-title":"Curr. Atheroscler. Rep."},{"key":"10.1016\/j.taap.2026.118047_bb0105","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1056\/NEJMoa1913805","article-title":"Inclisiran for the treatment of heterozygous familial hypercholesterolemia","volume":"382","author":"Raal","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.taap.2026.118047_bb0110","doi-asserted-by":"crossref","first-page":"75","DOI":"10.5334\/gh.1154","article-title":"World heart federation cholesterol roadmap 2022","volume":"17","author":"Ray","year":"2022","journal-title":"Glob. Heart"},{"key":"10.1016\/j.taap.2026.118047_bb0115","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1615664","article-title":"Evolocumab and clinical outcomes in patients with cardiovascular disease","volume":"376","author":"Sabatine","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.taap.2026.118047_bb0120","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1146\/annurev-physiol-032122-030352","article-title":"Fatty acid transport and signaling: mechanisms and physiological implications","volume":"85","author":"Samovski","year":"2023","journal-title":"Annu. Rev. Physiol."},{"key":"10.1016\/j.taap.2026.118047_bb0125","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa1801174","article-title":"Alirocumab and cardiovascular outcomes after acute coronary syndrome","volume":"379","author":"Schwartz","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.taap.2026.118047_bb0130","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1093\/cvr\/cvaa319","article-title":"The role of CD36 in cardiovascular disease","volume":"118","author":"Shu","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.taap.2026.118047_bb0135","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0239752","article-title":"PCSK9 loss of function is protective against extra-coronary atherosclerotic cardiovascular disease in a large multi-ethnic cohort","volume":"15","author":"Small","year":"2020","journal-title":"PLoS One"},{"key":"10.1016\/j.taap.2026.118047_bb0140","article-title":"PCSK9: a multi-faceted protein that is involved in cardiovascular biology","volume":"9","author":"Ss","year":"2021","journal-title":"Biomedicines"},{"key":"10.1016\/j.taap.2026.118047_bb0145","doi-asserted-by":"crossref","DOI":"10.1186\/s13104-019-4148-9","article-title":"Dyslipidemia and associated factors among women using hormonal contraceptives in Harar town, Eastern Ethiopia","volume":"12","author":"Sufa","year":"2019","journal-title":"BMC Res. Notes"},{"key":"10.1016\/j.taap.2026.118047_bb0150","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25179724","article-title":"Glucose-dependent insulinotropic polypeptide inhibits AGE-induced NADPH oxidase-derived oxidative stress generation and foam cell formation in macrophages partly via AMPK activation","volume":"25","author":"Terasaki","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.taap.2026.118047_bb0155","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.celrep.2018.12.022","article-title":"DHHC4 and DHHC5 facilitate fatty acid uptake by palmitoylating and targeting CD36 to the plasma membrane","volume":"26","author":"Wang","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.taap.2026.118047_bb0160","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/j.jacc.2022.07.006","article-title":"2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Solution set Oversight Committee","volume":"80","author":"Writing Committee","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"10.1016\/j.taap.2026.118047_bb0165","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.jhep.2018.04.006","article-title":"CD36 palmitoylation disrupts free fatty acid metabolism and promotes tissue inflammation in non-alcoholic steatohepatitis","volume":"69","author":"Zhao","year":"2018","journal-title":"J. Hepatol."}],"container-title":["Toxicology and Applied Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X26003431?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X26003431?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T21:51:15Z","timestamp":1793915475000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041008X26003431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":33,"alternative-id":["S0041008X26003431"],"URL":"https:\/\/doi.org\/10.1016\/j.taap.2026.118047","relation":{},"ISSN":["0041-008X"],"issn-type":[{"value":"0041-008X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Levonorgestrel-ethinyl estradiol impairs hepatic lipid clearance to induce hypercholesterolemia via PCSK9-mediated LDLR and CD36 dysregulation","name":"articletitle","label":"Article Title"},{"value":"Toxicology and Applied Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.taap.2026.118047","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118047"}}