{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T22:59:18Z","timestamp":1776898758432,"version":"3.51.2"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,5,30]],"date-time":"2021-05-30T00:00:00Z","timestamp":1622332800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,30]],"date-time":"2021-05-30T00:00:00Z","timestamp":1622332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012028","name":"Trombosestichting Nederland","doi-asserted-by":"publisher","award":["2018-1"],"award-info":[{"award-number":["2018-1"]}],"id":[{"id":"10.13039\/501100012028","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Thromb Thrombolysis"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Murine atherosclerosis models are key for investigation of atherosclerosis pathophysiology and drug development. However, they do not feature spontaneous atherothrombosis as a final stage of atherosclerosis. Transgenic mice expressing both the human mutant apolipoprotein E form <jats:italic>APOE*3-Leiden<\/jats:italic> and human cholesteryl ester transfer protein (<jats:italic>CETP<\/jats:italic>), i.e. <jats:italic>APOE*3-Leiden.CETP<\/jats:italic> mice, feature a moderate hyperlipoproteinemia and atherosclerosis phenotype. In contrast to apolipoprotein E deficient (<jats:italic>Apoe\u02c9<\/jats:italic><jats:sup><jats:italic>\/<\/jats:italic><\/jats:sup><jats:italic>\u02c9<\/jats:italic>) mice, <jats:italic>APOE*3-Leiden.CETP<\/jats:italic> mice respond well to lipid-lowering and anti-atherosclerotic drugs. The aim of the study was to investigate whether silencing of anticoagulant Protein C (<jats:italic>Proc<\/jats:italic>) allows <jats:italic>APOE*3-Leiden.CETP<\/jats:italic> mice to feature thrombosis as a final stage of atherosclerosis. Female <jats:italic>APOE*3-Leiden.CETP<\/jats:italic> mice were fed a Western-type diet to induce advanced atherosclerosis, followed by an injection with a small interfering RNA targeting <jats:italic>Proc<\/jats:italic> (si<jats:italic>Proc<\/jats:italic>). Presence of atherosclerosis and atherothrombosis was determined by histologic analysis of the aortic root. Atherosclerosis severity in the aortic root area of <jats:italic>APOE*3-Leiden.CETP<\/jats:italic> mice varied from type \u201c0\u201d (no lesions) to type \u201cV\u201d lesions (advanced and complex lesions). Atherothrombosis following si<jats:italic>Proc<\/jats:italic> injection was observed for 4 out of 21 <jats:italic>APOE*3-Leiden.CETP<\/jats:italic> mice (19% incidence). The atherothrombosis presented as large, organized, fibrin- and leukocyte-rich thrombi on top of advanced (type \u201cV\u201d) atherosclerotic plaques in the aortic root. This atherothrombosis was comparable in appearance and incidence as previously reported for <jats:italic>Apoe\u02c9<\/jats:italic><jats:sup><jats:italic>\/<\/jats:italic><\/jats:sup><jats:italic>\u02c9<\/jats:italic> mice with a more severe atherosclerosis (19% incidence). <jats:italic>APOE*3-Leiden.CETP<\/jats:italic> mice with modest hyperlipidemia and atherosclerosis can develop atherothrombosis upon transient <jats:italic>Proc<\/jats:italic>-silencing. This further extends the use of these mice as a test model for lipid-lowering and anti-atherosclerotic drugs.<\/jats:p>","DOI":"10.1007\/s11239-021-02488-2","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T09:14:41Z","timestamp":1624526081000},"page":"715-719","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Atherothrombosis model by silencing of protein C in APOE*3-Leiden.CETP transgenic mice"],"prefix":"10.1007","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1118-7005","authenticated-orcid":false,"given":"Yvonne K.","family":"Jongejan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeroen C. J.","family":"Eikenboom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion J. J.","family":"Gijbels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimmy F. P.","family":"Berb\u00e9e","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart J. M.","family":"van Vlijmen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,30]]},"reference":[{"key":"2488_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ejphar.2017.05.010","volume":"816","author":"B Emini Veseli","year":"2017","unstructured":"Emini Veseli B et al (2017) Animal models of atherosclerosis. 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JCJE declares to be financially supported by CSL Behring. The other authors declare no competing financial interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}