2-Hydroxypropyl-beta-cyclodextrin Treatment Does Not Induce Atherosclerotic Lesion Regression in Western-Type Diet-Fed Apolipoprotein E Knockout Mice
2-Hydroxypropyl-beta-cyclodextrin (2HPβCD) 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 regar...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/9/1205 |
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| author | Olga S.C. Snip Menno Hoekstra Yiheng Zhang Janine J. Geerling Miranda Van Eck |
| author_facet | Olga S.C. Snip Menno Hoekstra Yiheng Zhang Janine J. Geerling Miranda Van Eck |
| author_sort | Olga S.C. Snip |
| collection | DOAJ |
| description | 2-Hydroxypropyl-beta-cyclodextrin (2HPβCD) 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 2HPβCD to induce regression of established atherosclerotic lesions have been described. In the current study, we therefore also investigated the ability of 2HPβCD 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 2HPβCD 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 2HPβCD was not able to prevent the diet-switch-associated lesion growth or induce atherosclerosis regression. Although in our hands, 2HPβCD does effectively stimulate cellular cholesterol efflux from macrophages, we do not consider it worthwhile to further pursue 2HPβCD as therapeutic moiety in the atherosclerosis regression context. |
| first_indexed | 2024-03-10T00:37:04Z |
| format | Article |
| id | doaj.art-26f82ccad1024aa2bcaa767b307d2eb0 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T00:37:04Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-26f82ccad1024aa2bcaa767b307d2eb02023-11-23T15:14:39ZengMDPI AGBiomolecules2218-273X2022-08-01129120510.3390/biom120912052-Hydroxypropyl-beta-cyclodextrin Treatment Does Not Induce Atherosclerotic Lesion Regression in Western-Type Diet-Fed Apolipoprotein E Knockout MiceOlga S.C. Snip0Menno Hoekstra1Yiheng Zhang2Janine J. Geerling3Miranda Van Eck4Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The NetherlandsDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The NetherlandsDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The NetherlandsDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The NetherlandsDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands2-Hydroxypropyl-beta-cyclodextrin (2HPβCD) 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 2HPβCD to induce regression of established atherosclerotic lesions have been described. In the current study, we therefore also investigated the ability of 2HPβCD 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 2HPβCD 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 2HPβCD was not able to prevent the diet-switch-associated lesion growth or induce atherosclerosis regression. Although in our hands, 2HPβCD does effectively stimulate cellular cholesterol efflux from macrophages, we do not consider it worthwhile to further pursue 2HPβCD as therapeutic moiety in the atherosclerosis regression context.https://www.mdpi.com/2218-273X/12/9/1205cyclodextrincholesterol effluxmacrophagesatherosclerosis regressionmouse model |
| spellingShingle | Olga S.C. Snip Menno Hoekstra Yiheng Zhang Janine J. Geerling Miranda Van Eck 2-Hydroxypropyl-beta-cyclodextrin Treatment Does Not Induce Atherosclerotic Lesion Regression in Western-Type Diet-Fed Apolipoprotein E Knockout Mice Biomolecules cyclodextrin cholesterol efflux macrophages atherosclerosis regression mouse model |
| title | 2-Hydroxypropyl-beta-cyclodextrin Treatment Does Not Induce Atherosclerotic Lesion Regression in Western-Type Diet-Fed Apolipoprotein E Knockout Mice |
| title_full | 2-Hydroxypropyl-beta-cyclodextrin Treatment Does Not Induce Atherosclerotic Lesion Regression in Western-Type Diet-Fed Apolipoprotein E Knockout Mice |
| title_fullStr | 2-Hydroxypropyl-beta-cyclodextrin Treatment Does Not Induce Atherosclerotic Lesion Regression in Western-Type Diet-Fed Apolipoprotein E Knockout Mice |
| title_full_unstemmed | 2-Hydroxypropyl-beta-cyclodextrin Treatment Does Not Induce Atherosclerotic Lesion Regression in Western-Type Diet-Fed Apolipoprotein E Knockout Mice |
| title_short | 2-Hydroxypropyl-beta-cyclodextrin Treatment Does Not Induce Atherosclerotic Lesion Regression in Western-Type Diet-Fed Apolipoprotein E Knockout Mice |
| title_sort | 2 hydroxypropyl beta cyclodextrin treatment does not induce atherosclerotic lesion regression in western type diet fed apolipoprotein e knockout mice |
| topic | cyclodextrin cholesterol efflux macrophages atherosclerosis regression mouse model |
| url | https://www.mdpi.com/2218-273X/12/9/1205 |
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