雌激素通过 ER-α/CREB 抑制主动脉夹层中血管平滑肌细胞的表型转换

IF 4.3 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Yuting Pu, Yang Zhou, Tuo Guo, Xiangping Chai* and Guifang Yang*, 
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引用次数: 0

摘要

目的:通过ER-α/CREB通路抑制血管平滑肌细胞(VSMCs)表型转换,探讨主动脉夹层(AD)患者雌激素水平的变化及其对AD患者的保护作用。方法:收集人口统计学资料,评估AD患者的性别差异,并采用ELISA法检测血清17β-雌二醇(E2)水平。在AD患者和对照组的主动脉组织中分析表型转换标记。生物信息学分析确定了雌激素相关通路,重点是ER-α/CREB轴,并通过免疫组织化学和Western blot证实了表达水平。在雄性和去卵巢雌性小鼠中建立AD小鼠模型,评估E2补充对AD进展和VSMCs表型转换的影响。AD细胞模型也被用来通过靶向通路抑制来验证这些发现。结果:男性AD患病率较高,男性和绝经后女性患者血清E2水平均降低。切除卵巢的雌性小鼠AD发病率增加,而补充E2通过抑制VSMCs的表型转换来减少AD的进展。在AD患者中观察到ER-α和p-CREB/CREB表达下调,E2增强ER-α表达和CREB磷酸化,阻止VSMC表型转换。E2还促进ER-α/CREB相互作用,沉默ER-α抑制CREB磷酸化,导致VSMC表型转换增加。结论:雌激素(E2)通过ER-α/CREB信号通路维持VSMCs合成表型,在AD预防中发挥重要作用,对AD的发生具有保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Estrogen Inhibits the Phenotypic Switching of Vascular Smooth Muscle Cells through ER-α/CREB in Aortic Dissection

Objective: To examine the alterations in estrogen levels in patients with aortic dissection (AD) and its protective effect on AD patients through the inhibition of vascular smooth muscle cells (VSMCs) phenotypic switching via the ER-α/CREB pathway. Methods: Demographic data were collected to assess sex disparity in AD patients, and serum 17β-estradiol (E2) levels were measured using ELISA. Phenotypic switching markers were analyzed in aortic tissues from AD patients and controls. Bioinformatics analysis identified estrogen-related pathways, focusing on the ER-α/CREB axis, with expression levels confirmed via immunohistochemistry and Western blot. AD mouse models were developed in male and ovariectomized female mice, with the effects of E2 supplementation on AD progression and VSMCs phenotypic switching evaluated. An AD cellular model was also employed to verify these findings through targeted pathway inhibition. Results: AD prevalence was higher in males, with reduced serum E2 levels observed in both male and postmenopausal female patients. Ovariectomized female mice showed increased AD incidence, while E2 supplementation reduced AD progression by inhibiting the phenotypic switching of VSMCs. Downregulation of ER-α and p-CREB/CREB expression was observed in AD patients, and E2 enhanced ER-α expression and CREB phosphorylation, preventing VSMC phenotypic switching. E2 also promoted ER-α/CREB interaction, and silencing ER-α inhibited CREB phosphorylation, leading to increased VSMC phenotypic switching. Conclusions: Estrogen (E2) plays a crucial role in preventing AD by maintaining VSMCs synthetic phenotype through the ER-α/CREB signaling pathway, providing a protective effect against the development of AD.

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来源期刊
ACS Omega
ACS Omega Chemical Engineering-General Chemical Engineering
CiteScore
6.60
自引率
4.90%
发文量
3945
审稿时长
2.4 months
期刊介绍: ACS Omega is an open-access global publication for scientific articles that describe new findings in chemistry and interfacing areas of science, without any perceived evaluation of immediate impact.
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