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吸烟提取物通过Sirt1-SHH轴诱导HUVEC中的线粒体功能障碍和亡

Weiming Wang^1,2,3,4,5, Gang Yuan⁶, Guang Li³

¹Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, China.

Human & experimental toxicology

|April 2, 2025

概括

香烟吸烟提取物通过减少Sirt1和声波刺信号来诱导内皮细胞亡和线粒体功能障碍. 恢复Sirt1或激活sonic hedgehog可以防止与吸烟相关的内皮损伤和动脉样硬化.

科学领域:

心血管生物学心血管生物学
疾病的分子机制.
细胞和分子生理学细胞和分子生理学

背景情况:

众所周知,香烟吸烟提取物 (CSE) 会导致内皮细胞 (EC) 功能障碍,这是动脉样硬化发展的关键因素.
通过CSE诱导EC功能障碍的精确分子途径在很大程度上仍未被阐明.
脱乙酶Sirt1在EC生物过程中发挥着关键作用,这表明它参与了CSE诱导的损害.

研究的目的:

调查CSE是否通过Sirt1依赖机制诱导人类静脉内皮细胞 (HUVECs) 的亡和线粒体功能障碍.
探索声波刺 (SHH) 信号通路在CSE诱导的EC功能障碍中的作用.
评估CSE对活体动脉样硬化的影响以及Sirt1和SHH信号的参与.

主要方法:

在CSE治疗后评估了HUVEC活力,亡 (道染色) 和线粒体功能 (MitoTracker, JC-1).
利用lentiviral技术在HUVEC中过度表达Sirt1并评估SHH通路调节的影响.
在暴露于香烟烟雾的ApoE-knockout小鼠中评估动脉样硬化,分析大动脉组织的基因表达和脂质沉积 (油红色O染色).

主要成果:

CSE暴露降低了Sirt1和SHH表达,导致HUVEC亡和线粒体功能障碍.
过度表达Sirt1或激活SHH信号减弱了CSE诱导的细胞损伤.
抑制SHH信号传递取消了Sirt1过度表达的保护作用,表明存在功能联系.
在体内,CSE在ApoE-KO小鼠中加剧了动脉样硬化,降低了Sirt1,SHH和Gli1,并改变了Bax/Bcl-2表达.

结论:

通过抑制Sirt1表达和抑制SHH信号传递,CSE诱导内皮细胞线粒体功能障碍和亡.
Sirt1和SHH信号通路是内皮细胞对卷烟烟雾暴露反应的关键调解者.
这些发现为吸烟引起的动脉样硬化病原体和潜在的治疗点提供了新的见解.

关键词:

在Sirt1上灭症 (apoptosis) 是一种死亡的过程.香烟吸烟提取物香烟吸烟提取物内皮细胞是内皮细胞.线粒体功能障碍线粒体功能障碍

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