Oestrogen Inhibits Arterial Calcification by Promoting Autophagy

Abstract Arterial calcification is a major complication of cardiovascular disease. Oestrogen replacement therapy in postmenopausal women is associated with lower levels of coronary artery calcification, but its mechanism of action remains unclear. Here, we show that oestrogen inhibits the osteoblast...

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Autores principales:	Yi-Qun Peng, Dan Xiong, Xiao Lin, Rong-Rong Cui, Feng Xu, Jia-Yu Zhong, Ting Zhu, Feng Wu, Min-Zhi Mao, Xiao-Bo Liao, Ling-Qing Yuan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7ef4c6ec446740f8a8b59b8db7848a16
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spelling	oai:doaj.org-article:7ef4c6ec446740f8a8b59b8db7848a162021-12-02T16:06:32ZOestrogen Inhibits Arterial Calcification by Promoting Autophagy10.1038/s41598-017-03801-x2045-2322https://doaj.org/article/7ef4c6ec446740f8a8b59b8db7848a162017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03801-xhttps://doaj.org/toc/2045-2322Abstract Arterial calcification is a major complication of cardiovascular disease. Oestrogen replacement therapy in postmenopausal women is associated with lower levels of coronary artery calcification, but its mechanism of action remains unclear. Here, we show that oestrogen inhibits the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) in vitro and arterial calcification in vivo by promoting autophagy. Through electron microscopy, GFP–LC3 redistribution, and immunofluorescence analyses as well as measurement of the expression of the autophagosome marker light-chain I/II (LC3I/II) and autophagy protein 5 (Atg5), we show that autophagy is increased in VSMCs by oestrogen in vitro and in vivo. The inhibitory effect of oestrogen on arterial calcification was counteracted by 3-methyladenine (3MA) or knockdown of Atg5 and was increased by rapamycin. Furthermore, the inhibitory effect of oestrogen on arterial calcification and the degree of autophagy induced by oestrogen were blocked by a nonselective oestrogen receptor (ER) antagonist (ICI 182780), a selective oestrogen receptor alpha (ERα) antagonist (MPP), and ERα-specific siRNA. Our data indicate that oestrogen inhibits the osteoblastic differentiation of VSMCs by promoting autophagy through the ERα signalling pathway in vitro and arterial calcification in vivo by increasing autophagy. Our findings provide new insights into the mechanism by which oestrogen contributes to vascular calcification in vitro and in vivo.Yi-Qun PengDan XiongXiao LinRong-Rong CuiFeng XuJia-Yu ZhongTing ZhuFeng WuMin-Zhi MaoXiao-Bo LiaoLing-Qing YuanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yi-Qun Peng Dan Xiong Xiao Lin Rong-Rong Cui Feng Xu Jia-Yu Zhong Ting Zhu Feng Wu Min-Zhi Mao Xiao-Bo Liao Ling-Qing Yuan Oestrogen Inhibits Arterial Calcification by Promoting Autophagy
description	Abstract Arterial calcification is a major complication of cardiovascular disease. Oestrogen replacement therapy in postmenopausal women is associated with lower levels of coronary artery calcification, but its mechanism of action remains unclear. Here, we show that oestrogen inhibits the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) in vitro and arterial calcification in vivo by promoting autophagy. Through electron microscopy, GFP–LC3 redistribution, and immunofluorescence analyses as well as measurement of the expression of the autophagosome marker light-chain I/II (LC3I/II) and autophagy protein 5 (Atg5), we show that autophagy is increased in VSMCs by oestrogen in vitro and in vivo. The inhibitory effect of oestrogen on arterial calcification was counteracted by 3-methyladenine (3MA) or knockdown of Atg5 and was increased by rapamycin. Furthermore, the inhibitory effect of oestrogen on arterial calcification and the degree of autophagy induced by oestrogen were blocked by a nonselective oestrogen receptor (ER) antagonist (ICI 182780), a selective oestrogen receptor alpha (ERα) antagonist (MPP), and ERα-specific siRNA. Our data indicate that oestrogen inhibits the osteoblastic differentiation of VSMCs by promoting autophagy through the ERα signalling pathway in vitro and arterial calcification in vivo by increasing autophagy. Our findings provide new insights into the mechanism by which oestrogen contributes to vascular calcification in vitro and in vivo.
format	article
author	Yi-Qun Peng Dan Xiong Xiao Lin Rong-Rong Cui Feng Xu Jia-Yu Zhong Ting Zhu Feng Wu Min-Zhi Mao Xiao-Bo Liao Ling-Qing Yuan
author_facet	Yi-Qun Peng Dan Xiong Xiao Lin Rong-Rong Cui Feng Xu Jia-Yu Zhong Ting Zhu Feng Wu Min-Zhi Mao Xiao-Bo Liao Ling-Qing Yuan
author_sort	Yi-Qun Peng
title	Oestrogen Inhibits Arterial Calcification by Promoting Autophagy
title_short	Oestrogen Inhibits Arterial Calcification by Promoting Autophagy
title_full	Oestrogen Inhibits Arterial Calcification by Promoting Autophagy
title_fullStr	Oestrogen Inhibits Arterial Calcification by Promoting Autophagy
title_full_unstemmed	Oestrogen Inhibits Arterial Calcification by Promoting Autophagy
title_sort	oestrogen inhibits arterial calcification by promoting autophagy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7ef4c6ec446740f8a8b59b8db7848a16
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_version_	1718384971886886912

Oestrogen Inhibits Arterial Calcification by Promoting Autophagy

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