血管光滑肌细胞中的YAP/TAZ缺失反映了动脉样硬化相关的转录程序
Fatima Daoud1,2, Johan Holmberg1, Hanna Winter3,4
1Department of Experimental Medical Science, Lund University, 22184, Lund, Sweden.
Journal of molecular and cellular cardiology plus
|November 17, 2025
概括
在血管光滑肌细胞 (VSMC) 中删除YAP/TAZ会导致动脉样变化. YAP/TAZ通常可以防止VSMC脱差,炎症和斑块的形成,突出显示YAP/TAZ-TEAD轴作为治疗点.
科学领域:
- 血管生物学 血管生物学
- 分子生物学分子生物学
- 心血管研究研究心血管研究
背景情况:
- 血管光滑肌细胞 (VSMC) 现型对于血管平衡至关重要.
- 转录辅助激活剂YAP (YAP1) 和TAZ (WWTR1) 调节VSMC的身份.
- 动脉样硬化涉及VSMC脱差和斑块形成.
研究的目的:
- 调查YAP/TAZ在VSMC表型维护中的作用.
- 确定VSMC特定的YAP/TAZ删除对动脉样硬化发展的影响.
- 确定将YAP/TAZ与血管疾病联系起来的分子机制.
主要方法:
- 在小鼠中YAP/TAZ的VSMC特异性删除.
- 大量和单细胞RNA测序 (scRNA-seq) 分析.
- ChIP-seq和促销者动机分析.
- 与人类和小鼠动脉样硬化病变的转录组比较.
主要成果:
- 在VSMC中YAP/TAZ删除回顾了动脉样硬化的主要特征.
- 基因表达的变化反映了动脉样硬化斑块的发展,特别是在8周.
- 在YAP/TAZ缺乏VSMC中的下调基因包括那些参与肌肉收缩和细胞骨完整性的基因.
- 升级的途径包括炎症,细胞外矩阵重塑,和chondrogenic分化.
- YAP/TAZ损失诱导了VSMC的表型转向类似于冠状肌细胞和类似于纤维肌细胞的状态.
- 19个保存的YAP-TEAD标基因被抑制,其中一些也在动脉样硬化斑块中降低调节.
结论:
- YAP/TAZ对于维护VSMC身份和防止脱差至关重要.
- 破坏YAP/TAZ信号传递促进了VSMC中的炎症和骨质质原生程序.
- 通过改变VSMC表型,YAP/TAZ损失有助于动脉动脉生成.
- YAP/TAZ-TEAD轴是血管平衡的关键调节器,也是动脉样硬化的潜在治疗点.
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