BMAL1 缺陷增加了胸前大动脉动脉瘤和剖析风险
Wenyu Song1, Guangguo Fu1, Qing Li2
1Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Cardiovascular research
|November 21, 2025
概括
由于BMAL1缺乏症通过REV-ERBα增加血管光滑肌细胞 (VSMC) 亡,使胸前大动脉动脉瘤和解剖 (TAAD) 恶化. 向BMAL1和REV-ERBα可能提供新的TAAD疗法.
科学领域:
- 心血管生物学 心血管生物学
- 分子遗传学 分子遗传学
- 时间生物学 时间生物学
背景情况:
- 血管光滑肌细胞 (VSMC) 亡在胸腔大动脉动脉瘤和解剖 (TAAD) 的发展中至关重要.
- BMAL1失调与亡有关,但其在TAAD病变发生中的作用尚不清楚.
研究的目的:
- 研究BMAL1在TAAD发育中的作用及其对VSMC亡的影响.
- 阐明BMAL1在TAAD中的功能背后的分子机制.
主要方法:
- 在TAAD患者和小鼠模型 (BAPN诱导) 中进行转录基因分析.
- 使用了全球性和VSMC特定的BMAL1哈普洛因不足小鼠.
- 进行了组织学,空间转录学和体外实验.
主要成果:
- 在TAAD患者和小鼠中观察到降低的BMAL1水平.
- BMAL1 缺陷加剧了TAAD 和VSMC 亡.
- BMAL1调节REV-ERBα,这反过来又控制了诱导亡的c-MYC.
- BMAL1激活剂和REV-ERBα激动剂显示出治疗潜力.
结论:
- 通过REV-ERBα下调调节诱导VSMC亡,BMAL1不足促进TAAD.
- BMAL1和REV-ERBα是TAAD预防和治疗的有希望的药理学标.
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