Effects of 17β-estradiol and equilin on atherosclerosis development in female Apoe shl mice

Abstract The effects of conjugated equine estrogens (CEE) and 17β-estradiol-based hormone replacement therapy (HRT) on atherosclerosis development remain controversial. Here, we investigated the effects of equilin, a major compound in CEE, and 17β-estradiol on atherosclerosis development in an ather...

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Main Authors: Akiyo Kakibuchi, Fumitake Ito, Osamu Takaoka, Nanami Tahara, Mari Kawamata, Kazuya Yabumoto, Akihisa Katayama, Yuko Izumi, Eiko Maeda, Taisuke Mori
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-10494-0
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author Akiyo Kakibuchi
Fumitake Ito
Osamu Takaoka
Nanami Tahara
Mari Kawamata
Kazuya Yabumoto
Akihisa Katayama
Yuko Izumi
Eiko Maeda
Taisuke Mori
author_facet Akiyo Kakibuchi
Fumitake Ito
Osamu Takaoka
Nanami Tahara
Mari Kawamata
Kazuya Yabumoto
Akihisa Katayama
Yuko Izumi
Eiko Maeda
Taisuke Mori
author_sort Akiyo Kakibuchi
collection DOAJ
description Abstract The effects of conjugated equine estrogens (CEE) and 17β-estradiol-based hormone replacement therapy (HRT) on atherosclerosis development remain controversial. Here, we investigated the effects of equilin, a major compound in CEE, and 17β-estradiol on atherosclerosis development in an atherosclerotic mouse model. Female B6.KOR/StmSlc-Apoe shl mice were ovariectomized and fed a high-fat diet for 9 and 12 weeks (early and late groups, respectively) and then treated with 17β-estradiol or equilin. Atherosclerotic lesions in the aortic arch and brachiocephalic artery (BCA) were assessed at the end of the experimental period. Compared with placebo, equilin and 17β-estradiol significantly inhibited atherosclerotic lesion formation in the aortic arch and BCA in both groups. However, 17β-estradiol had a significantly greater inhibitory effect than equilin in the late group. Although 17β-estradiol significantly inhibited atherosclerosis progression in the aortic root, no significant difference was observed between the equilin and placebo groups. Additionally, compared with equilin, 17β-estradiol significantly inhibited atherosclerotic plaque formation in the aortic root. Moreover, 17β-estradiol exerted a stronger inhibitory effect on atherogenesis than equilin and control. Both 17β-estradiol and equilin protect against atherosclerotic plaque formation in the vascular endothelium, with 17β-estradiol exhibiting a superior effect.
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spelling doaj-art-1e22d3d9538f49b6b7a80985f30debf62025-08-20T03:05:26ZengNature PortfolioScientific Reports2045-23222025-07-011511810.1038/s41598-025-10494-0Effects of 17β-estradiol and equilin on atherosclerosis development in female Apoe shl miceAkiyo Kakibuchi0Fumitake Ito1Osamu Takaoka2Nanami Tahara3Mari Kawamata4Kazuya Yabumoto5Akihisa Katayama6Yuko Izumi7Eiko Maeda8Taisuke Mori9Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineAbstract The effects of conjugated equine estrogens (CEE) and 17β-estradiol-based hormone replacement therapy (HRT) on atherosclerosis development remain controversial. Here, we investigated the effects of equilin, a major compound in CEE, and 17β-estradiol on atherosclerosis development in an atherosclerotic mouse model. Female B6.KOR/StmSlc-Apoe shl mice were ovariectomized and fed a high-fat diet for 9 and 12 weeks (early and late groups, respectively) and then treated with 17β-estradiol or equilin. Atherosclerotic lesions in the aortic arch and brachiocephalic artery (BCA) were assessed at the end of the experimental period. Compared with placebo, equilin and 17β-estradiol significantly inhibited atherosclerotic lesion formation in the aortic arch and BCA in both groups. However, 17β-estradiol had a significantly greater inhibitory effect than equilin in the late group. Although 17β-estradiol significantly inhibited atherosclerosis progression in the aortic root, no significant difference was observed between the equilin and placebo groups. Additionally, compared with equilin, 17β-estradiol significantly inhibited atherosclerotic plaque formation in the aortic root. Moreover, 17β-estradiol exerted a stronger inhibitory effect on atherogenesis than equilin and control. Both 17β-estradiol and equilin protect against atherosclerotic plaque formation in the vascular endothelium, with 17β-estradiol exhibiting a superior effect.https://doi.org/10.1038/s41598-025-10494-0Hormone replacement therapy (HRT)AtherosclerosisEstrogenEquilinEn face analysisAortic root analysis
spellingShingle Akiyo Kakibuchi
Fumitake Ito
Osamu Takaoka
Nanami Tahara
Mari Kawamata
Kazuya Yabumoto
Akihisa Katayama
Yuko Izumi
Eiko Maeda
Taisuke Mori
Effects of 17β-estradiol and equilin on atherosclerosis development in female Apoe shl mice
Scientific Reports
Hormone replacement therapy (HRT)
Atherosclerosis
Estrogen
Equilin
En face analysis
Aortic root analysis
title Effects of 17β-estradiol and equilin on atherosclerosis development in female Apoe shl mice
title_full Effects of 17β-estradiol and equilin on atherosclerosis development in female Apoe shl mice
title_fullStr Effects of 17β-estradiol and equilin on atherosclerosis development in female Apoe shl mice
title_full_unstemmed Effects of 17β-estradiol and equilin on atherosclerosis development in female Apoe shl mice
title_short Effects of 17β-estradiol and equilin on atherosclerosis development in female Apoe shl mice
title_sort effects of 17β estradiol and equilin on atherosclerosis development in female apoe shl mice
topic Hormone replacement therapy (HRT)
Atherosclerosis
Estrogen
Equilin
En face analysis
Aortic root analysis
url https://doi.org/10.1038/s41598-025-10494-0
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