LncRNA RP4-639F20.1/THRAP3途径介导AngII对血管平滑肌细胞增殖迁移和动脉粥样硬化的影响及机制研究

血管平滑肌细胞增殖迁移是影响动脉粥样硬化（AS）进展的关键步骤。血管紧张素II（AngII）通过调节血管平滑肌细胞增殖迁移影响AS进展，但其机制尚不明了。预实验结果显示AS斑块组织中lncRNA RP4-639F20.1表达下调，AngII下调血管平滑肌细胞RP4-639F20.1表达水平，RP4-639F20.1可以与THRAP3结合，过表达RP4-639F20.1抑制血管平滑肌细胞THRAP3表达，敲减THRAP3表达可抑制血管平滑肌细胞增殖迁移。因此我们提出RP4-639F20.1/THRAP3途径介导AngII影响血管平滑肌细胞增殖迁移和AS进展。本项目拟通过增强/抑制RP4-639F20.1和/或THRAP3表达，观察RP4-639F20.1/THRAP3途径介导AngII对血管平滑肌细胞增殖迁移和AS的影响并探讨相关机制，为确定该途径作为防治AS的新靶点提供科学依据。

Vascular smooth muscle cell (VSMC) proliferation and migration play a key role in atherosclerosis progression. Angiotensin II (Ang II) can regulate VSMC proliferation and migration, thereby influencing atherosclerosis progression; however, the underlying mechanisms are still not fully understood. Our preliminary study showed that atherosclerotic plaques expressed the long non-coding RNA (IncRNA) RP4-639F20.1, Ang II reduced RP4-639F20.1 expression in VSMCs, RP4-639F20.1 interacted with thyroid hormone receptor associated protein 3 (THRAP3), RP4-639F20.1 inhibited THRAP3 expression in VSMCs, and THRAP3 knockdown resulted in reduced VSMC proliferation and migration. Therefore, we hypothesize that the RP4-639F20.1/THRAP3 pathway mediates the effect of Ang II on VSMC proliferation/migration and atherosclerosis progression. This project will further elucidate the role of the RP4-639F20.1/THRAP3 pathway in VSMC proliferation/migration and atherosclerosis progression, providing a better mechanistic understanding of this pathway as a potential therapeutic target.