血管平滑肌细胞（VSMCs）的增殖与迁移在动脉粥样硬化（As）的发生发展中起关键作用。RNA结合蛋白QKI与肿瘤细胞的增殖分化密切相关，并可作用于VSMCs特异性转录因子心肌素（Myocardin），影响VSMCs的增殖分化。我们前期研究发现，GSK-3β能通过对心肌素的磷酸化调控VSMCs的增殖分化，当VSMCs增殖时，QKI和心肌素-v1增多，而维持VMSCs呈收缩态的心肌素-v3减少。因此提出假设：QKI可通过选择性剪接心肌素pre-mRNA调节VSMCs表型转化，影响As进程。本项目拟使用前期构建的稳定表达心肌素的VSMCs深入研究QKI对心肌素及VSMCs表型转化的作用机制；并构建高度拟人化的新型As仓鼠模型，研究QKI在体内能否调节VSMCs表型转化来影响As进程；从分子-细胞-动物多层面研究QKI调控心肌素对As发生发展的作用机制，以期为As的防治提供新的治疗靶点及理论依据。

The proliferation and migration of vascular smooth muscle cells (VSMCs) play a key role in the occurrence and development of atherosclerosis(As). It was reported that RNA-binding protein QKI is closely related to the proliferation and differentiation of tumor cells and can influence the proliferation and differentiation of VSMCs by acting on Myocardin, the specific transcription factor of VSMCs. Our previous studies showed that GSK-3β could regulate the proliferation and differentiation of VSMCs through the phosphorylation of Myocardin. Besides, QKI and Myocardin -v1 was increased when the proliferation activity of VSMCs was enhanced, while Myocardin-v3, which maintained the contractile state of VSMCs,was decreased. So we hypothesized that: QKI can regulate the phenotypic transformation of VSMCs through selective splicing of Myocardin pre-mRNA, and can influence the pathological changes of As. We intend to use previously constructed VSMCs that can stably expresse Myocardin to study whether QKI can regulate VSMCs phenotypic transformation by regulating Myocardin and how it works. Meanwhile, a new type of As model of hamster is applied to explore whether QKI can regulate the phenotypic transformation of VSMCs and can influence the pathological changes of As. In short, our goal is to make sure whethe and how QKI can regulate Myocardin and affect on AS. It will be systematically explored from three aspects of molecule-cell-animal in order to provide a new idea and therapeutic target for the prevention and treatment of As.