17β-Estradiol Inhibits Proliferation and Oxidative Stress in Vascular Smooth Muscle Cells by Upregulating BHLHE40 Expression
Background: Intimal hyperplasia is a major complication of restenosis after angioplasty. The abnormal proliferation and oxidative stress of vascular smooth muscle cells (VSMCs) are the basic pathological feature of neointimal hyperplasia. 17β-Estradiol can inhibit VSMCs proliferation and inflammatio...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:01c03860a7cb4d3283a4ded710c033152021-12-01T15:58:26Z17β-Estradiol Inhibits Proliferation and Oxidative Stress in Vascular Smooth Muscle Cells by Upregulating BHLHE40 Expression2297-055X10.3389/fcvm.2021.768662https://doaj.org/article/01c03860a7cb4d3283a4ded710c033152021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.768662/fullhttps://doaj.org/toc/2297-055XBackground: Intimal hyperplasia is a major complication of restenosis after angioplasty. The abnormal proliferation and oxidative stress of vascular smooth muscle cells (VSMCs) are the basic pathological feature of neointimal hyperplasia. 17β-Estradiol can inhibit VSMCs proliferation and inflammation. However, it is still unclear whether and how 17β-Estradiol affects intimal hyperplasia.Methods: The neointima hyperplasia was observed by hematoxylin/eosin staining. The expression of PCNA, cyclin D1, NOX1, NOX4 and p47phox in neointima hyperplasia tissues and VSMCs was determined by qRT-PCR and Western blotting. MTS assay, cell counting and EdU staining were performed to detect cells proliferation. The oxidative stress was assessed by ROS staining.Results: 17β-Estradiol suppressed carotid artery ligation-induced intimal hyperplasia, which is accompanied by an increase of BHLHE40 level. Furthermore, loss- and gain-of-function experiments revealed that BHLHE40 knockdown promotes, whereas BHLHE40 overexpression inhibits TNF-α-induced VSMC proliferation and oxidative stress. 17β-Estradiol inhibited TNF-α-induced VSMC proliferation and oxidative stress by promoting BHLHE40 expression, thereby suppressing MAPK signaling pathways. In addition, enforcing the expression of BHLHE40 leads to amelioration of intimal hyperplasia.Conclusions: Our study demonstrates that 17β-Estradiol inhibits proliferation and oxidative stress in vivo and in vitro by promotion of BHLHE40 expression.Dan-dan FengBin ZhengJing YuJing YuMan-li ZhangMan-li ZhangYing MaYing MaXiao HaoJin-kun WenXin-hua ZhangFrontiers Media S.A.article17β-EstradiolVSMCsBHLHE40proliferationoxidative stressDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021) |
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| topic |
17β-Estradiol VSMCs BHLHE40 proliferation oxidative stress Diseases of the circulatory (Cardiovascular) system RC666-701 |
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17β-Estradiol VSMCs BHLHE40 proliferation oxidative stress Diseases of the circulatory (Cardiovascular) system RC666-701 Dan-dan Feng Bin Zheng Jing Yu Jing Yu Man-li Zhang Man-li Zhang Ying Ma Ying Ma Xiao Hao Jin-kun Wen Xin-hua Zhang 17β-Estradiol Inhibits Proliferation and Oxidative Stress in Vascular Smooth Muscle Cells by Upregulating BHLHE40 Expression |
| description |
Background: Intimal hyperplasia is a major complication of restenosis after angioplasty. The abnormal proliferation and oxidative stress of vascular smooth muscle cells (VSMCs) are the basic pathological feature of neointimal hyperplasia. 17β-Estradiol can inhibit VSMCs proliferation and inflammation. However, it is still unclear whether and how 17β-Estradiol affects intimal hyperplasia.Methods: The neointima hyperplasia was observed by hematoxylin/eosin staining. The expression of PCNA, cyclin D1, NOX1, NOX4 and p47phox in neointima hyperplasia tissues and VSMCs was determined by qRT-PCR and Western blotting. MTS assay, cell counting and EdU staining were performed to detect cells proliferation. The oxidative stress was assessed by ROS staining.Results: 17β-Estradiol suppressed carotid artery ligation-induced intimal hyperplasia, which is accompanied by an increase of BHLHE40 level. Furthermore, loss- and gain-of-function experiments revealed that BHLHE40 knockdown promotes, whereas BHLHE40 overexpression inhibits TNF-α-induced VSMC proliferation and oxidative stress. 17β-Estradiol inhibited TNF-α-induced VSMC proliferation and oxidative stress by promoting BHLHE40 expression, thereby suppressing MAPK signaling pathways. In addition, enforcing the expression of BHLHE40 leads to amelioration of intimal hyperplasia.Conclusions: Our study demonstrates that 17β-Estradiol inhibits proliferation and oxidative stress in vivo and in vitro by promotion of BHLHE40 expression. |
| format |
article |
| author |
Dan-dan Feng Bin Zheng Jing Yu Jing Yu Man-li Zhang Man-li Zhang Ying Ma Ying Ma Xiao Hao Jin-kun Wen Xin-hua Zhang |
| author_facet |
Dan-dan Feng Bin Zheng Jing Yu Jing Yu Man-li Zhang Man-li Zhang Ying Ma Ying Ma Xiao Hao Jin-kun Wen Xin-hua Zhang |
| author_sort |
Dan-dan Feng |
| title |
17β-Estradiol Inhibits Proliferation and Oxidative Stress in Vascular Smooth Muscle Cells by Upregulating BHLHE40 Expression |
| title_short |
17β-Estradiol Inhibits Proliferation and Oxidative Stress in Vascular Smooth Muscle Cells by Upregulating BHLHE40 Expression |
| title_full |
17β-Estradiol Inhibits Proliferation and Oxidative Stress in Vascular Smooth Muscle Cells by Upregulating BHLHE40 Expression |
| title_fullStr |
17β-Estradiol Inhibits Proliferation and Oxidative Stress in Vascular Smooth Muscle Cells by Upregulating BHLHE40 Expression |
| title_full_unstemmed |
17β-Estradiol Inhibits Proliferation and Oxidative Stress in Vascular Smooth Muscle Cells by Upregulating BHLHE40 Expression |
| title_sort |
17β-estradiol inhibits proliferation and oxidative stress in vascular smooth muscle cells by upregulating bhlhe40 expression |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/01c03860a7cb4d3283a4ded710c03315 |
| work_keys_str_mv |
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