{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T18:47:04Z","timestamp":1776106024130,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T00:00:00Z","timestamp":1426464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["Grant 91813603"],"award-info":[{"award-number":["Grant 91813603"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["2008T070 \/ 2012T080"],"award-info":[{"award-number":["2008T070 \/ 2012T080"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,5]]},"abstract":"Background and Purpose<\/jats:title>Antipsychotic drugs have been shown to modulate the expression of ATP<\/jats:styled-content>\u2010binding cassette transporter A1<\/jats:styled-content> (ABCA1<\/jats:styled-content>), a key factor in the anti\u2010atherogenic reverse cholesterol transport process, in vitro<\/jats:italic>. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro<\/jats:italic> and their susceptibility to atherosclerosis in vivo<\/jats:italic>.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Thioglycollate\u2010elicited peritoneal macrophages were used for in vitro<\/jats:italic> studies. Hyperlipidaemic low\u2010density lipoprotein (LDL<\/jats:styled-content>) receptor knockout mice were implanted with a haloperidol\u2010containing pellet and subsequently fed a W<\/jats:styled-content>estern\u2010type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo<\/jats:italic>.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Haloperidol induced a 54% decrease in the mRNA<\/jats:styled-content> expression of ABCA1<\/jats:styled-content> in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1<\/jats:styled-content>. Haloperidol treatment stimulated the expression of ABCA1<\/jats:styled-content> (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1<\/jats:styled-content> (+98%) in livers of LDL<\/jats:styled-content> receptor knockout mice. No change in splenic ABCA1<\/jats:styled-content> expression was noted. However, the average size of the atherosclerotic size was significantly smaller (\u221231%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP<\/jats:styled-content>\u20101 expression (\u221270%) and secretion (\u221228%) by peritoneal macrophages.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL<\/jats:styled-content> receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13067","type":"journal-article","created":{"date-parts":[[2015,1,9]],"date-time":"2015-01-09T11:43:23Z","timestamp":1420803803000},"page":"2397-2405","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Haloperidol inhibits the development of atherosclerotic lesions in LDL<\/scp> receptor knockout mice"],"prefix":"10.1111","volume":"172","author":[{"given":"Ronald J","family":"van der Sluis","sequence":"first","affiliation":[{"name":"Division of Biopharmaceutics Cluster of BioTherapeutics Leiden Academic Centre for Drug Research Gorlaeus Laboratories Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joya E","family":"Nahon","sequence":"additional","affiliation":[{"name":"Division of Biopharmaceutics Cluster of BioTherapeutics Leiden Academic Centre for Drug Research Gorlaeus Laboratories Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Q","family":"Reuwer","sequence":"additional","affiliation":[{"name":"Laboratory for Microbiology and Infection Control Amphia Hospital Breda The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda","family":"Van Eck","sequence":"additional","affiliation":[{"name":"Division of Biopharmaceutics Cluster of BioTherapeutics Leiden Academic Centre for Drug Research Gorlaeus Laboratories Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menno","family":"Hoekstra","sequence":"additional","affiliation":[{"name":"Division of Biopharmaceutics Cluster of BioTherapeutics Leiden Academic Centre for Drug Research Gorlaeus Laboratories Leiden The 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