{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:06Z","timestamp":1787027766904,"version":"build-2736575974"},"reference-count":14,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Netherlands Organization for Scientific Research VICI","award":["91813603"],"award-info":[{"award-number":["91813603"]}]},{"name":"The Netherlands Organization for Scientific Research VICI","award":["2007T056"],"award-info":[{"award-number":["2007T056"]}]},{"DOI":"10.13039\/501100002996","name":"Dutch Heart Foundation","doi-asserted-by":"publisher","award":["91813603"],"award-info":[{"award-number":["91813603"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Dutch Heart Foundation","doi-asserted-by":"publisher","award":["2007T056"],"award-info":[{"award-number":["2007T056"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>2-Hydroxypropyl-beta-cyclodextrin (2HP\u03b2CD) is able to bind and solubilize unesterified cholesterol and may therefore be able to reverse the deposition of cholesterol in macrophages within the aortic vessel wall, a hallmark of atherosclerotic cardiovascular disease. However, conflicting results regarding the potential of 2HP\u03b2CD to induce regression of established atherosclerotic lesions have been described. In the current study, we therefore also investigated the ability of 2HP\u03b2CD to stimulate cholesterol removal from macrophage foam cells in vitro and induce the regression of established atherosclerotic lesions in apolipoprotein E knockout (APOE KO) mice. In vitro studies using murine thioglycollate-elicited peritoneal macrophages verified that 2HP\u03b2CD is able to induce cholesterol efflux from macrophages in an ATP-binding cassette transporter-independent manner. Switching Western-type-diet-fed APOE KO mice with established atherosclerotic lesions back to a chow diet was associated with a reduction in the hypercholesterolemia extent and an increase in the absolute lesion size and plaque collagen-to-macrophage ratio. Importantly, parallel subcutaneous administration of 2HP\u03b2CD was not able to prevent the diet-switch-associated lesion growth or induce atherosclerosis regression. Although in our hands, 2HP\u03b2CD does effectively stimulate cellular cholesterol efflux from macrophages, we do not consider it worthwhile to further pursue 2HP\u03b2CD as therapeutic moiety in the atherosclerosis regression context.<\/jats:p>","DOI":"10.3390\/biom12091205","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T23:53:21Z","timestamp":1661990001000},"page":"1205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["2-Hydroxypropyl-beta-cyclodextrin Treatment Does Not Induce Atherosclerotic Lesion Regression in Western-Type Diet-Fed Apolipoprotein E Knockout Mice"],"prefix":"10.3390","volume":"12","author":[{"given":"Olga S.C.","family":"Snip","sequence":"first","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7463-2893","authenticated-orcid":false,"given":"Menno","family":"Hoekstra","sequence":"additional","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"},{"name":"Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"},{"name":"Pharmacy Leiden, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine J.","family":"Geerling","sequence":"additional","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda","family":"Van Eck","sequence":"additional","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"},{"name":"Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"},{"name":"Pharmacy Leiden, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"ref_1","first-page":"57","article-title":"Arterial foam cells with distinctive immunomorphologic and histochemical features of macrophages","volume":"100","author":"Schaffner","year":"1980","journal-title":"Am. J. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Cholesterol Treatment Trialists\u2019 (CTT) Collaboration, Fulcher, J., O\u2019Connell, R., Voysey, M., Emberson, J., Blackwell, L., Mihaylova, B., Simes, J., Collins, R., and Kirby, A. (2015). Efficacy and safety of LDL-lowering therapy among men and women: Meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet, 385, 1397\u20131405.","DOI":"10.1016\/S0140-6736(14)61368-4"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0022-2275(20)41534-2","article-title":"Bile acid and sterol solubilization in 2-hydroxypropyl-beta-cyclodextrin","volume":"33","author":"Yun","year":"1992","journal-title":"J. Lipid Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"333ra50","DOI":"10.1126\/scitranslmed.aad6100","article-title":"Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming","volume":"8","author":"Zimmer","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jconrel.2019.12.021","article-title":"Cyclodextrin polymer improves atherosclerosis therapy and reduces ototoxicity","volume":"319","author":"Kim","year":"2020","journal-title":"J. Control. Release."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1161\/01.ATV.0000237629.29842.4c","article-title":"Macrophage ABCG1 deletion disrupts lipid homeostasis in alveolar macrophages and moderately influences atherosclerotic lesi\u00f3n development in LDL receptor-deficient mice","volume":"26","author":"Out","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"24020","DOI":"10.1074\/jbc.R114.583658","article-title":"Molecular mechanisms of cellular cholesterol efflux","volume":"289","author":"Phillips","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"716357","DOI":"10.3389\/fimmu.2021.716357","article-title":"Pro-Inflammatory Implications of 2-Hydroxypropyl-\u03b2-cyclodextrin Treatment","volume":"12","author":"Houben","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"586980","DOI":"10.3389\/fendo.2020.586980","article-title":"Downregulation of Cyp7a1 by Cholic Acid and Chenodeoxycholic Acid in Cyp27a1\/ApoE Double Knockout Mice: Differential Cardiovascular Outcome","volume":"11","author":"Zurkinden","year":"2020","journal-title":"Front. Endocrinol (Lausanne)."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"57008","DOI":"10.1289\/EHP8171","article-title":"Sex-Specific Effects of Prenatal and Early Life Inorganic and Methylated Arsenic Exposure on Atherosclerotic Plaque Development and Composition in Adult ApoE-\/- Mice","volume":"129","author":"Makhani","year":"2021","journal-title":"Environ. Health Perspect."},{"key":"ref_11","first-page":"309","article-title":"Increased aortic atherosclerotic plaque development in female apolipoprotein E-null mice is associated with elevated thromboxane A2 and decreased prostacyclin production","volume":"61","author":"Smith","year":"2010","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1161\/01.ATV.0000051387.70962.79","article-title":"Expansive remodeling is a response of the plaque-related vessel wall in aortic roots of apoE-deficient mice: An experiment of nature","volume":"23","author":"Bentzon","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e131","DOI":"10.1161\/ATV.0000000000000062","article-title":"3rd, Rosenfeld, M.E.; Virmani, R.; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; and Council on Basic Cardiovascular Sciences. 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_14","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.joca.2012.02.010","article-title":"Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research","volume":"20","author":"Kilkenny","year":"2012","journal-title":"Osteoarthr. 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