Resveratrol Ameliorates Aortic Calcification in Ovariectomized Rats via SIRT1 Signaling
Postmenopausal women are at an increased risk of vascular calcification which is defined as the pathological deposition of minerals in the vasculature, and is strongly linked with increased cardiovascular disease risk. Since estrogen-replacement therapy is associated with increased cancer risk, ther...
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MDPI AG
2021-09-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/43/2/75 |
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| author | Sally K. Hammad Rana G. Eissa Mohamed A. Shaheen Nahla N. Younis |
| author_facet | Sally K. Hammad Rana G. Eissa Mohamed A. Shaheen Nahla N. Younis |
| author_sort | Sally K. Hammad |
| collection | DOAJ |
| description | Postmenopausal women are at an increased risk of vascular calcification which is defined as the pathological deposition of minerals in the vasculature, and is strongly linked with increased cardiovascular disease risk. Since estrogen-replacement therapy is associated with increased cancer risk, there is a strong need for safer therapeutic approaches. In this study we aimed to investigate the protective and therapeutic effects of the phytoestrogen resveratrol against vascular calcification in ovariectomized rats, a preclinical model of postmenopause. Furthermore, we aimed to compare the effects of resveratrol to those of estrogen and to explore the mechanisms underpinning those effects. Treatment with resveratrol or estrogen ameliorated aortic calcification in ovariectomized rats, as shown by reduced calcium deposition in the arterial wall. Mechanistically, the effects of resveratrol and estrogen were mediated via the activation of SIRT1 signaling. SIRT1 protein expression was downregulated in the aortas of ovariectomized rats, and upregulated in rats treated with resveratrol or estrogen. Moreover, resveratrol and estrogen reduced the levels of the osteogenic markers: runt-related transcription factor 2 (RUNX2), osteocalcin and alkaline phosphatase (ALP) which have been shown to play a role during vascular calcification. Additionally, the senescence markers (p53, p16 and p21) which were also reported to play a role in the pathogenesis of vascular calcification, were reduced upon treatment with resveratrol and estrogen. In conclusion, the phytoestrogen resveratrol may be a safer alternative to estrogen, as a therapeutic approach against the progression of vascular calcification during postmenopause. |
| first_indexed | 2024-03-10T07:47:20Z |
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| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-10T07:47:20Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
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| series | Current Issues in Molecular Biology |
| spelling | doaj.art-564318f9e43b41fd9009f638d337acbc2023-11-22T12:31:22ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452021-09-014321057107110.3390/cimb43020075Resveratrol Ameliorates Aortic Calcification in Ovariectomized Rats via SIRT1 SignalingSally K. Hammad0Rana G. Eissa1Mohamed A. Shaheen2Nahla N. Younis3Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig 44519, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptPostmenopausal women are at an increased risk of vascular calcification which is defined as the pathological deposition of minerals in the vasculature, and is strongly linked with increased cardiovascular disease risk. Since estrogen-replacement therapy is associated with increased cancer risk, there is a strong need for safer therapeutic approaches. In this study we aimed to investigate the protective and therapeutic effects of the phytoestrogen resveratrol against vascular calcification in ovariectomized rats, a preclinical model of postmenopause. Furthermore, we aimed to compare the effects of resveratrol to those of estrogen and to explore the mechanisms underpinning those effects. Treatment with resveratrol or estrogen ameliorated aortic calcification in ovariectomized rats, as shown by reduced calcium deposition in the arterial wall. Mechanistically, the effects of resveratrol and estrogen were mediated via the activation of SIRT1 signaling. SIRT1 protein expression was downregulated in the aortas of ovariectomized rats, and upregulated in rats treated with resveratrol or estrogen. Moreover, resveratrol and estrogen reduced the levels of the osteogenic markers: runt-related transcription factor 2 (RUNX2), osteocalcin and alkaline phosphatase (ALP) which have been shown to play a role during vascular calcification. Additionally, the senescence markers (p53, p16 and p21) which were also reported to play a role in the pathogenesis of vascular calcification, were reduced upon treatment with resveratrol and estrogen. In conclusion, the phytoestrogen resveratrol may be a safer alternative to estrogen, as a therapeutic approach against the progression of vascular calcification during postmenopause.https://www.mdpi.com/1467-3045/43/2/75menopausevascular calcificationestrogenphytoestrogenresveratrolpolyphenol |
| spellingShingle | Sally K. Hammad Rana G. Eissa Mohamed A. Shaheen Nahla N. Younis Resveratrol Ameliorates Aortic Calcification in Ovariectomized Rats via SIRT1 Signaling Current Issues in Molecular Biology menopause vascular calcification estrogen phytoestrogen resveratrol polyphenol |
| title | Resveratrol Ameliorates Aortic Calcification in Ovariectomized Rats via SIRT1 Signaling |
| title_full | Resveratrol Ameliorates Aortic Calcification in Ovariectomized Rats via SIRT1 Signaling |
| title_fullStr | Resveratrol Ameliorates Aortic Calcification in Ovariectomized Rats via SIRT1 Signaling |
| title_full_unstemmed | Resveratrol Ameliorates Aortic Calcification in Ovariectomized Rats via SIRT1 Signaling |
| title_short | Resveratrol Ameliorates Aortic Calcification in Ovariectomized Rats via SIRT1 Signaling |
| title_sort | resveratrol ameliorates aortic calcification in ovariectomized rats via sirt1 signaling |
| topic | menopause vascular calcification estrogen phytoestrogen resveratrol polyphenol |
| url | https://www.mdpi.com/1467-3045/43/2/75 |
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