Oestrogen Inhibits Arterial Calcification by Promoting Autophagy.
Oestrogen Inhibits Arterial Calcification by Promoting Autophagy.
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雌激素通过促进自噬抑制动脉钙化
DOI：
10.1038/s41598-017-03801-x
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发表时间：
2017-06-14
影响因子：
4.6
通讯作者：
Yuan LQ
中科院分区：
文献类型：
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作者：
Peng YQ;Xiong D;Lin X;Cui RR;Xu F;Zhong JY;Zhu T;Wu F;Mao MZ;Liao XB;Yuan LQ
动脉钙化是心血管疾病的主要并发症。绝经后妇女的雌激素替代疗法与较低水平的冠状动脉钙化有关，但其作用机制尚不清楚。在这里，我们发现雌激素通过促进自噬来抑制体外培养的血管平滑肌细胞(VSMCs)的成骨分化和体内动脉的钙化。通过电子显微镜、GFP-LC3重分布、免疫荧光分析以及自噬标记轻链I/II(LC3I/II)和自噬蛋白5(ATG5)表达的测定，我们发现雌激素在体外和体内都增加了VSMC的自噬。雌激素对动脉钙化的抑制作用可被3-甲基腺嘌呤(3MA)或ATG5基因敲除所抵消，并被雷帕霉素增强。此外，雌激素对动脉钙化和自噬程度的抑制作用可被非选择性雌激素受体拮抗剂(ICI 182780)、选择性雌激素受体α(ERα)拮抗剂和ERα特异性小干扰RNA所阻断。我们的数据表明，雌激素在体外通过ER-α信号通路促进自噬，在体内通过增加自噬促进动脉钙化，从而抑制血管平滑肌细胞的成骨分化。我们的发现为雌激素在体外和体内促进血管钙化的机制提供了新的见解。
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 vitroand arterial calcificationin vivoby 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 oestrogenin vitroandin 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 pathwayin vitroand arterial calcificationin vivoby increasing autophagy. Our findings provide new insights into the mechanism by which oestrogen contributes to vascular calcificationin vitroandin vivo.