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机械传感器Piezo1介导的光滑肌细胞灭导致血管化

Jun Tao¹, Daiting You¹, Zejiang Feng¹

¹Department of Pathophysiology, School of Medicine, Shenzhen Campus of Sun Yat‑sen University, Shenzhen, Guangdong 518107, P.R. China.

International journal of molecular medicine

|September 12, 2025

概括

机械传感器通道Piezo1通过触发光滑肌肉细胞死亡来促进血管化. 抑制Piezo1减少了动脉中的积累,为血管疾病提供了潜在的治疗标.

科学领域:

心血管生物学心血管生物学
机械生物学机械生物学
细胞生理学细胞生理学

背景情况:

血管化与慢性炎症和光滑肌肉细胞 (SMC) 变化有关.
驱动血管化的精确机制尚未完全理解.
像Piezo1这样的机械传感器通道正在成为细胞过程的关键调节者.

研究的目的:

调查机械传感器通道Piezo1在血管SMC死亡和血管化的作用.
阐明Piezo1通过影响这些过程的分子途径.

主要方法:

在人类和小鼠动脉样硬化斑块中Piezo1表达的分析.
在体外研究使用培养的VSMC和暴露在化介质 (CM) 的动脉环.
药理上抑制/激活Piezo1,基因删除研究 (Piezo1,NLRP3,caspase1,gasdermin D) 和免疫沉测定.
在慢性病环境中使用VSMC特定的Piezo1淘汰赛小鼠模型进行体内验证.

主要成果:

在动脉样硬化斑块中,Piezo1表达升高.
CM增加了Piezo1和RUNX2的表达,诱导了VSMC热,并促进了沉积,由Piezo1活动调节的效果.
对NLRP3,caspase1或gasdermin D的遗传删除可以减少CM诱导的热和化.
皮埃佐1通过CaMKII与RUNX2相互作用,而CaMKII抑制减弱了热和化.
在小鼠模型中,特定于VSMC的Piezo1删除可以防止动脉化.

结论:

皮埃佐1是血管化的关键调节者.
Piezo1通过Ca2+-CaMKII依赖的NLRP3炎症体的激活来调解VSMC热和随后的血管化.
准Piezo1可能为血管化提供一种新的治疗策略.

关键词:

含有3个NLR家族pyrin域的NLR家族pyrin域.这是一个Piezo1.动脉化是一种动脉化.卡尔/卡尔莫杜林依赖的蛋白激酶II.热致灭 (pyroptosis) 是一种致的过程.血管光滑肌肉细胞的细胞.

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