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在双主动脉关联的胸前主动脉动脉瘤中,FOXO1驱动的内皮衰老

Miqi Zhou¹, Minjie Hu¹, Lu Ding¹

¹Department of Cell Biology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325015, Zhejiang, China.

Biochimica et biophysica acta. Molecular basis of disease

|September 19, 2025

概括

内皮细胞衰老有助于胸前大动脉动脉瘤 (BAV-TAA) 的双主动脉. 针对FOXO1通路可能为BAV-TAA提供新的治疗策略.

科学领域:

心血管生物学心血管生物学
干细胞生物学干细胞生物学
遗传学是一个遗传学.

背景情况:

双动脉 (BAV) 是一种与胸前动脉动脉瘤 (TAA) 相关的先天性心脏缺陷.
内皮功能障碍与BAV-TAA病原发生有关,内皮细胞衰老是关键标志物.
缺乏将内皮老化与BAV-TAA联系起来的直接证据.

研究的目的:

调查内皮细胞衰老在BAV-TAA中的作用.
探索FOXO信号通路在BAV-TAA相关的内皮细胞衰老中的参与.
评估FOXO1抑制作为BAV-TAA的潜在治疗策略.

主要方法:

从BAV-TAA患者和对照中产生诱导多能干细胞 (iPSC).
区分iPSCs成内皮细胞 (iECs) 进行比较分析.
利用RNA测序进行转录基因分析,并确定了关键信号通路.
用一个FOXO1抑制剂 (AS1842856) 来评估其治疗效果.

主要成果:

由BAV-TAA衍生的iECs表现出显著的衰老表型,包括减少的增殖和迁移,以及增加的衰老标志物 (p53,p21,p16).
在BAV-TAA-iEC中观察到明显的衰老相关分泌表现型 (SASP).
在BAV-TAA-iEC中发现了FOXO信号通路的异常激活.
抑制FOXO1可以逆转衰老,恢复eNOS表达,减少SASP,并通过p65和p38通道减轻炎症.

结论:

内皮细胞衰老是BAV-TAA的病变发生的一个关键因素.
FOXO信号通路与BAV-TAA相关的内皮细胞衰老有关.
针对FOXO1信号提供了一个有前途的治疗途径,用于BAV-TAA和相关的大动脉疾病.

关键词:

双主动脉 (BAV) 是一个双主动脉.内皮老化的内皮衰老.在FOXO信号通道中,诱导多能干细胞 (iPSCs) 是一种干细胞.胸前大动脉动脉瘤 (TAA) 发生

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