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Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagy.

Authors
  • Meng, Qinghai1
  • Li, Yu2
  • Ji, Tingting1
  • Chao, Ying1
  • Li, Jun1
  • Fu, Yu1
  • Wang, Suyun1
  • Chen, Qi1
  • Chen, Wen3
  • Huang, Fuhua3
  • Wang, Youran3
  • Zhang, Qichun1, 4
  • Wang, Xiaoliang5
  • Bian, Huimin1, 4
  • 1 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. , (China)
  • 2 School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. , (China)
  • 3 Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210023, China. , (China)
  • 4 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. , (China)
  • 5 Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210023, China. , (China)
Type
Published Article
Journal
Journal of advanced research
Publication Date
Feb 01, 2021
Volume
28
Pages
149–164
Identifiers
DOI: 10.1016/j.jare.2020.08.010
PMID: 33364052
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Excessive inflammation and the pyroptosis of vascular endothelial cells caused by estrogen deficiency is one cause of atherosclerosis in post-menopausal women. Because autophagy is highly regulated by estrogen, we hypothesized that estrogen can reduce vascular endothelial cell pyroptosis through estrogen receptor alpha (ERα)-mediated activation of autophagy to improve atherosclerosis in post-menopausal stage. 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. 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. Thus, 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. © 2020 The Authors. Published by Elsevier B.V. on behalf of Cairo University.

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