Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagy
Introduction: Excessive inflammation and the pyroptosis of vascular endothelial cells caused by estrogen deficiency is one cause of atherosclerosis in post-menopausal women. The autophagy is highly regulated by estrogen, however whether estrogen can reduce vascular endothelial cell pyroptosis throug...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2021-02-01
|
Series: | Journal of Advanced Research |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123220301983 |
id |
doaj-ec908c511bdf4e6abc416782be7c7d4d |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qinghai Meng Yu Li Tingting Ji Ying Chao Jun Li Yu Fu Suyun Wang Qi Chen Wen Chen Fuhua Huang Youran Wang Qichun Zhang Xiaoliang Wang Huimin Bian |
spellingShingle |
Qinghai Meng Yu Li Tingting Ji Ying Chao Jun Li Yu Fu Suyun Wang Qi Chen Wen Chen Fuhua Huang Youran Wang Qichun Zhang Xiaoliang Wang Huimin Bian Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagy Journal of Advanced Research Menopause Estrogen Atherosclerosis Autophagy Inflammation Pyroptosis |
author_facet |
Qinghai Meng Yu Li Tingting Ji Ying Chao Jun Li Yu Fu Suyun Wang Qi Chen Wen Chen Fuhua Huang Youran Wang Qichun Zhang Xiaoliang Wang Huimin Bian |
author_sort |
Qinghai Meng |
title |
Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagy |
title_short |
Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagy |
title_full |
Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagy |
title_fullStr |
Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagy |
title_full_unstemmed |
Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagy |
title_sort |
estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagy |
publisher |
Elsevier |
series |
Journal of Advanced Research |
issn |
2090-1232 |
publishDate |
2021-02-01 |
description |
Introduction: Excessive inflammation and the pyroptosis of vascular endothelial cells caused by estrogen deficiency is one cause of atherosclerosis in post-menopausal women. The autophagy is highly regulated by estrogen, however whether estrogen can reduce vascular endothelial cell pyroptosis through estrogen receptor-mediated activation of autophagy to improve atherosclerosis in post-menopausal stage is still unknown. Objectives: To explore whether estrogen can prevent atherosclerosis by regulating estrogen receptor and subsequently activating autophagy to reduce inflammation and pyroptosis. Methods: Aortic samples from pro-menopausal and post-menopausal women with ascending aortic arteriosclerosis were analyzed, and bilateral ovariectomized (OVX) female ApoE-/- mice and homocysteine (Hcy)-treated HUVECs were used to analyze the effect of estrogen supplementation therapy. Results: The aortic endothelium showed a decrease in ERα expression and autophagy, but presented an increase in inflammation and pyroptosis in female post-menopausal patients. Estrogen treatment accelerated autophagy and ameliorated cell pyroptosis in the cardiac aortas of OVX ApoE-/- mice and Hcy-treated HUVECs. Estrogen had therapeutic effect on atherosclerosis and improved the symptoms associated with lipid metabolism disorders in OVX ApoE-/- mice. Inhibition and silencing of ERα led to a reduction in the autophagy promoting ability of estrogen and aggravated pyroptosis. Moreover, the inhibition of autophagy promoted pyroptosis and abolished the protective effect of estrogen, but had no influence on ERα expression. Conclusion: The results of the present study demonstrated that post-menopausal women present decreased autophagy and ERα expression and excessive damage to the ascending aorta. In addition, in vitro and in vivo assay results demonstrated that estrogen prevents atherosclerosis by upregulating ERα expression and subsequently induces autophagy to reduce inflammation and pyroptosis. |
topic |
Menopause Estrogen Atherosclerosis Autophagy Inflammation Pyroptosis |
url |
http://www.sciencedirect.com/science/article/pii/S2090123220301983 |
work_keys_str_mv |
AT qinghaimeng estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT yuli estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT tingtingji estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT yingchao estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT junli estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT yufu estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT suyunwang estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT qichen estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT wenchen estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT fuhuahuang estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT youranwang estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT qichunzhang estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT xiaoliangwang estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy AT huiminbian estrogenpreventatherosclerosisbyattenuatingendothelialcellpyroptosisviaactivationofestrogenreceptoramediatedautophagy |
_version_ |
1724269348835557376 |
spelling |
doaj-ec908c511bdf4e6abc416782be7c7d4d2021-02-15T04:13:12ZengElsevierJournal of Advanced Research2090-12322021-02-0128149164Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagyQinghai Meng0Yu Li1Tingting Ji2Ying Chao3Jun Li4Yu Fu5Suyun Wang6Qi Chen7Wen Chen8Fuhua Huang9Youran Wang10Qichun Zhang11Xiaoliang Wang12Huimin Bian13School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaDepartment of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210023, ChinaDepartment of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210023, ChinaDepartment of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210023, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaDepartment of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210023, China; Corresponding authors at: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China (H. Bian). Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210023, China (X. Wang).School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Corresponding authors at: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China (H. Bian). Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210023, China (X. Wang).Introduction: Excessive inflammation and the pyroptosis of vascular endothelial cells caused by estrogen deficiency is one cause of atherosclerosis in post-menopausal women. The autophagy is highly regulated by estrogen, however whether estrogen can reduce vascular endothelial cell pyroptosis through estrogen receptor-mediated activation of autophagy to improve atherosclerosis in post-menopausal stage is still unknown. Objectives: To explore whether estrogen can prevent atherosclerosis by regulating estrogen receptor and subsequently activating autophagy to reduce inflammation and pyroptosis. Methods: Aortic samples from pro-menopausal and post-menopausal women with ascending aortic arteriosclerosis were analyzed, and bilateral ovariectomized (OVX) female ApoE-/- mice and homocysteine (Hcy)-treated HUVECs were used to analyze the effect of estrogen supplementation therapy. Results: The aortic endothelium showed a decrease in ERα expression and autophagy, but presented an increase in inflammation and pyroptosis in female post-menopausal patients. Estrogen treatment accelerated autophagy and ameliorated cell pyroptosis in the cardiac aortas of OVX ApoE-/- mice and Hcy-treated HUVECs. Estrogen had therapeutic effect on atherosclerosis and improved the symptoms associated with lipid metabolism disorders in OVX ApoE-/- mice. Inhibition and silencing of ERα led to a reduction in the autophagy promoting ability of estrogen and aggravated pyroptosis. Moreover, the inhibition of autophagy promoted pyroptosis and abolished the protective effect of estrogen, but had no influence on ERα expression. Conclusion: The results of the present study demonstrated that post-menopausal women present decreased autophagy and ERα expression and excessive damage to the ascending aorta. In addition, in vitro and in vivo assay results demonstrated that estrogen prevents atherosclerosis by upregulating ERα expression and subsequently induces autophagy to reduce inflammation and pyroptosis.http://www.sciencedirect.com/science/article/pii/S2090123220301983MenopauseEstrogenAtherosclerosisAutophagyInflammationPyroptosis |