{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:50:16Z","timestamp":1791816616847,"version":"4.3.4"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Maxwell Biotech Group"},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00c3\u00bcr Bildung und Forschung","doi-asserted-by":"publisher","award":["VIP+ 03VP01020"],"award-info":[{"award-number":["VIP+ 03VP01020"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Bile acids are known to have a positive impact on atherosclerosis. The study investigates the impact of sodium taurocholate co-transporting polypeptide (NTCP) inhibition with bulevirtide, organic anion transporting polypeptide (OATP) inhibition with rifampicin, and their combination on bile acid levels and atherosclerosis in apolipoprotein E\u2013deficient (ApoE\u207b\/\u207b) mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Fifty-six female ApoE\u207b\/\u207b\u2009mice on a Western type diet were treated daily for four weeks with bulevirtide (5\u2009mg\/kg), rifampicin (20\u2009mg\/kg), a combination of both, or vehicle. Plasma bile acids and lipids were measured at sacrifice. Atherosclerotic lesion size was quantified in the aortic sinus, and macrophage content was\u00a0analyzed\u00a0by Mac-2 immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Plasma cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels remained unchanged across all groups, being accompanied with no changes of atherosclerotic lesion size (p\u2009=\u20090.896). However, treatment with bulevirtide (p\u2009=\u20090.017), rifampicin (p\u2009=\u20090.003), but mostly their combination (p\u2009&lt;\u20090.001) significantly increased plasma bile acid concentrations and altered the macrophage-to-lesion area ratio, at least for the combination therapy group (p\u2009=\u20090.020). The combined treatment exhibited the highest bile acid levels, indicating additive effects of dual transporter inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>While lesion sizes remained unaffected, the combined NTCP and OATP inhibition significantly enhanced bile acid levels and reduced macrophage content in early atherosclerotic lesions of ApoE\u207b\/\u207b\u2009mice. These results highlight the association of bile acid with the modulation of plaque composition as a potential therapeutic mode of action.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0349211","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T17:27:02Z","timestamp":1779816422000},"page":"e0349211","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of bulevirtide on atherosclerosis in an ApoE-deficient mouse 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