血流动力学是促进新生内膜形成的关键因素，但力学因素如何诱导内膜新生的机制不清。生物信息学分析发现，在目前已报道的机械力门控通道中，仅Piezo1通道的表达在新生内膜中明显上调。预实验结果显示，人和小鼠新生内膜中Piezo1的表达水平显著升高，敲减Piezo1可明显抑制新生内膜形成。机制分析发现激活Piezo1可上调YAP/TAZ的表达。据此我们提出假设：即Piezo1-YAP/TAZ信号通路是血流动力学紊乱诱导新生内膜形成的关键机制。本研究拟进一步采用Piezo1血管平滑肌条件敲除小鼠，首先明确Piezo1通道在新生内膜形成中的作用，进而阐明YAP/TAZ是否是Piezo1激活的关键下游分子，并揭示Piezo1调控YAP/TAZ表达的机理。工作将从Piezo1-YAP/TAZ角度揭示血流动力学紊乱诱导新生内膜形成的新机制，为明确Piezo1是否是防治新生内膜形成的有效新靶点提供理论依据。

Hemodynamic factors play a crucial role in the process of neointimal hyperplasia, but the molecular basis of its biomechanical receptors is still unclear. Analysis of the database results found that among the mechanically-gated channels reported so far, only the expression of Piezo1 channel was significantly up-regulated in the neointimal. Our previous results show that the expression level of Piezo1 in neonatal intima of humans and mice is significantly increased, and knockdown of Piezo1 can significantly inhibit neointimal formation. Mechanism analysis found that the activation of Piezo1 can up-regulate the expression of YAP/TAZ. Based on this, we propose the hypothesis that the Piezo1-YAP/TAZ signaling pathway is a key mechanism for hemodynamic disturbance to induce neointimal formation. This study intends to further use Piezo1 vascular smooth muscle conditional knockout mice to first clarify the role of the Piezo1 channel in neointimal formation, and to clarify whether YAP/TAZ is a key downstream molecule for the activation of Piezo1, and reveal the mechanism that Piezo1 regulates the expression of YAP/TAZ. The work will reveal the new mechanism of hemodynamic disturbance-induced neointimal formation from the perspective of Piezo1-YAP/TAZ, and provide a theoretical basis for clarifying whether Piezo1 is an effective new target for the prevention and treatment of neointimal formation.