A Timing Effect of 17-β Estradiol on Atherosclerotic Lesion Development in Female ApoE<sup>−/−</sup> Mice
Differences in size or composition of existing plaques at the initiation of estrogen (E2) therapy may underpin evidence of increased risk of atherosclerosis-associated clinical sequelae. We investigated whether E2 had divergent effects on actively-growing versus established-advanced atherosclerotic...
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/13/4710 |
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| author | Obialunanma V. Ebenebe Zoe Ashley Jeffrey R. Erickson Alison K. Heather |
| author_facet | Obialunanma V. Ebenebe Zoe Ashley Jeffrey R. Erickson Alison K. Heather |
| author_sort | Obialunanma V. Ebenebe |
| collection | DOAJ |
| description | Differences in size or composition of existing plaques at the initiation of estrogen (E2) therapy may underpin evidence of increased risk of atherosclerosis-associated clinical sequelae. We investigated whether E2 had divergent effects on actively-growing versus established-advanced atherosclerotic lesions. Eight weeks of subcutaneous bi-weekly injections of 3 µg/g 17β-estradiol (<i>n</i> = 18) or vehicle control (<i>n</i> = 22) were administered to female Apolipoprotein null-mice aged 25- or 45 weeks old. Histological assessment of lesion size within the brachiocephalic artery was conducted. Lesion composition was also assessed with acellular, calcification and fibrosis areas measured and other cellular features (intimal thickening, foam cells, lipid pools and cholesterol) scored (0–3) for severity. The comparison showed increased lesion size and calcified area with advancing age but no effect of E2. However, subtle changes in composition were observed following E2. Within the younger group, E2 increased intima thickening and acceleration of calcification. In the older group, E2 increased the thickness of the lesion cap. Therefore, this study shows different effects of E2 depending on the underlying stage of lesion development at the time of initiation of treatment. These divergent changes help explain the controversy of the adverse effects of E2 treatment in cardiovascular disease. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:45:00Z |
| publishDate | 2020-07-01 |
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| spelling | doaj.art-ecbe35fde37e4deeb5e774ab6ce5aaf22023-11-20T05:35:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012113471010.3390/ijms21134710A Timing Effect of 17-β Estradiol on Atherosclerotic Lesion Development in Female ApoE<sup>−/−</sup> MiceObialunanma V. Ebenebe0Zoe Ashley1Jeffrey R. Erickson2Alison K. Heather3Department of Physiology and Heart Otago, School of Biomedical Sciences, University of Otago, Dunedin 9054, New ZealandDepartment of Physiology and Heart Otago, School of Biomedical Sciences, University of Otago, Dunedin 9054, New ZealandDepartment of Physiology and Heart Otago, School of Biomedical Sciences, University of Otago, Dunedin 9054, New ZealandDepartment of Physiology and Heart Otago, School of Biomedical Sciences, University of Otago, Dunedin 9054, New ZealandDifferences in size or composition of existing plaques at the initiation of estrogen (E2) therapy may underpin evidence of increased risk of atherosclerosis-associated clinical sequelae. We investigated whether E2 had divergent effects on actively-growing versus established-advanced atherosclerotic lesions. Eight weeks of subcutaneous bi-weekly injections of 3 µg/g 17β-estradiol (<i>n</i> = 18) or vehicle control (<i>n</i> = 22) were administered to female Apolipoprotein null-mice aged 25- or 45 weeks old. Histological assessment of lesion size within the brachiocephalic artery was conducted. Lesion composition was also assessed with acellular, calcification and fibrosis areas measured and other cellular features (intimal thickening, foam cells, lipid pools and cholesterol) scored (0–3) for severity. The comparison showed increased lesion size and calcified area with advancing age but no effect of E2. However, subtle changes in composition were observed following E2. Within the younger group, E2 increased intima thickening and acceleration of calcification. In the older group, E2 increased the thickness of the lesion cap. Therefore, this study shows different effects of E2 depending on the underlying stage of lesion development at the time of initiation of treatment. These divergent changes help explain the controversy of the adverse effects of E2 treatment in cardiovascular disease.https://www.mdpi.com/1422-0067/21/13/4710atherosclerosiscalcificationfibrosisintimal thickeningmenopauseestrogen therapy |
| spellingShingle | Obialunanma V. Ebenebe Zoe Ashley Jeffrey R. Erickson Alison K. Heather A Timing Effect of 17-β Estradiol on Atherosclerotic Lesion Development in Female ApoE<sup>−/−</sup> Mice International Journal of Molecular Sciences atherosclerosis calcification fibrosis intimal thickening menopause estrogen therapy |
| title | A Timing Effect of 17-β Estradiol on Atherosclerotic Lesion Development in Female ApoE<sup>−/−</sup> Mice |
| title_full | A Timing Effect of 17-β Estradiol on Atherosclerotic Lesion Development in Female ApoE<sup>−/−</sup> Mice |
| title_fullStr | A Timing Effect of 17-β Estradiol on Atherosclerotic Lesion Development in Female ApoE<sup>−/−</sup> Mice |
| title_full_unstemmed | A Timing Effect of 17-β Estradiol on Atherosclerotic Lesion Development in Female ApoE<sup>−/−</sup> Mice |
| title_short | A Timing Effect of 17-β Estradiol on Atherosclerotic Lesion Development in Female ApoE<sup>−/−</sup> Mice |
| title_sort | timing effect of 17 β estradiol on atherosclerotic lesion development in female apoe sup sup mice |
| topic | atherosclerosis calcification fibrosis intimal thickening menopause estrogen therapy |
| url | https://www.mdpi.com/1422-0067/21/13/4710 |
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