过早的细胞衰老促进了血管光滑肌肉细胞的表型调节和抵抗重新分化的抵抗力
Anuradha Kaistha1, Sebnem Oc1, Abel Martin Garrido1
1From the Section of Cardiorespiratory Medicine, University of Cambridge.
Cardiovascular research
|June 10, 2025
概括
DNA损伤导致血管光滑肌细胞 (VSMC) 衰老,通过阻碍VSMC重新分化来促进动脉样硬化. 衰老的VSMCs表达非分化的标记物,有助于血管疾病的进展.
科学领域:
- 心血管生物学 心血管生物学
- 细胞衰老 细胞衰老
- 血管光滑肌肉细胞生物学
背景情况:
- 人类动脉硬性斑块细胞中的DNA损伤可能导致过早衰老.
- 血管光滑肌细胞 (VSMC) 衰老与动脉动脉发生,不稳定的斑块和新内形成有关.
- 通过VSMC衰老促进血管疾病和改变VSMC表型的确切机制尚不清楚.
研究的目的:
- 调查VSMC过早衰老如何影响血管疾病的发展.
- 确定衰老对VSMC表型和基因表达的影响.
- 为了阐明参与衰老驱动的VSMC功能障碍的分子途径.
主要方法:
- 大量和单细胞RNA测序人类和小鼠VSMCs.
- 来自带有诱导过早衰老 (TRF2T188A) 的谱系追踪小鼠的VSMCs的分析.
- 研究基因表达,细胞表型和信号通路激活 (例如TGF-β,STING-TBK1-IRF3).
主要成果:
- 衰老诱导了去差异化的VSMC标记物 (例如,TNFRSF11B,FMOD,TMEM178B,SFRP4) 和抑制的收缩标记物的上调.
- 在小鼠中,过早衰老导致动脉样硬化增加,脱差分标记和TGF-β信号失调.
- 衰老的VSMC表现出细胞质DNA,激活了STING-TBK1-IRF3通路,并抑制了TGF-β信号;IRF3抑制恢复了TGF-β通路组件和收缩标记.
结论:
- DNA损伤和衰老诱导了非差异化/纤维肌细胞VSMC表型,这种表型在体内持续存在.
- 衰老的VSMC在重新分化过程中无法重新表达收缩标记物.
- 大型中小细胞衰老可能通过损害大型中小细胞重新分化来促进动脉样硬化和新亲密形成.
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