牵张调控血管平滑肌细胞（VSMC）的增殖迁移等功能，与血管疾病的发生发展密切相关。离子通道TRPC1及所介导的钙流SOCE与VSMC的增殖迁移和内膜增厚等血管病征呈正相关。TRPC1在质膜上的凹陷—小窝（Caveolae）内的定位调节其特性及所介导的SOCE的活性。小窝结构又受牵张影响。由此提出科学问题：牵张是否通过Caveolae影响TRPC1-SOCE的活性进而实现对VSMC功能的调控？目前相关研究未见报道。鉴于此，本项目拟开展Caveolae对TRPC1-SOCE的影响在周期性牵张调控VSMC增殖迁移中的作用及机制研究，并应用扫描电镜、膜片钳、钙成像、免疫共沉淀等技术重点研究：1）牵张是否以及如何通过Caveolae影响TRPC1-SOCE的活性；2）这种影响在牵张调控VSMC增殖迁移中的作用及机制。以期为深入理解力学致VSMC功能变化的机制、找寻心血管疾病治疗的靶标提供生物力学依据

Stretch influences the proliferation and migration of vascular smooth muscle cells (VSMC), further leads to cardiovascular diseases. Canonical transient receptor potential 1 (TRPC1) and its mediated store-operated calcium entry (SOCE) play an important role in proliferation and migration of VSMCs and the development of cardiovascular diseases such as neointimal hyperplasia. The localization of TRPC1 with caveolae regulates its characteristics and its mediated SOCE. Furthermore, caveolae is disssembled or assembled responded to stretch. Then raised a question: whether mechanical stretch influences TRPC1 and its mediated SOCE through caveolae, further stretch-regulated VSMC function ? This question has not been answered till today. .This project focuses on the “the role and underlying mechanism of caveolae-impacted TRPC1-SOCE in cyclic stretch-regulated proliferation and migration of VSMCs”, and will investigate: 1) whether and how mechanical stretch influences TRPC1 and its mediated SOCE through caveolae; 2) the role and underlying mechanism of that influence in stretch-regulated alteration of VSMC function, using scanning microscopy, patch clamp, calcium image, as well as co-immunoprecipitation. This study is aimed to provide insight into understanding the mechanism by which cyclic stretch influences the VSMC function and finding novel therapeutic strategy for cardiovascular disease.