平滑肌细胞Piezo1对于表型转换和新极端增生症至关重要
Fei-Ran Zhang1,2, Jie Tang2, Ying Lai2
1Program of Kidney and Cardiovascular Diseases, the Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
机械敏感的Piezo1通道在neointima上升调节,并驱动血管光滑肌肉细胞的增殖,导致neointimal增生. 向Piezo1为隐蔽性血管疾病提供了潜在的治疗策略.
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
- 血管生物学 血管生物学
背景情况:
- 动乱的血液流动会触发血管光滑肌细胞 (VSMC) 的激活和新极端增生.
- 已知机械传感器Piezo1通道对于血管发育至关重要,但其在VSMC介导的新内密形成中的作用尚不清楚.
研究的目的:
- 调查Piezo1通道在VSMCs在新极端增生症发展期间的功能作用.
主要方法:
- 在人类冠状动脉新密和小鼠模型中检查了Piezo1表达 (造植入,导线损伤).
- 使用VSMC特定的Piezo1淘汰赛小鼠进行体内和体外功能研究.
- 研究了涉及YAP,TAZ和Ca2+的下游信号通路.
主要成果:
- 与中间层相比,Piezo1表达在VSMC丰富的neointima中显著上调.
- 特定于VSMC的Piezo1淘汰在小鼠模型中显著降低了neointimal增生症.
- 通过YAP/TAZ路径,Piezo1激活促进,而缺乏抑制,通过YAP/TAZ路径扰乱流动诱导的VSMC增殖,迁移和合成表型切换.
结论:
- 机械敏感的Piezo1通道关键调节VSMC表型,并有助于新极端增生.
- 准Piezo1为治疗不适应性血管改造和封闭性血管疾病提供了一种新的治疗途径.
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