Ca2+依赖的Calcineurin/NFATc1信号通路参与并调节机体内多种心血管相关疾病，但在钙化性主动脉瓣膜病(CAVD)中的作用机制尚不明确。我们前期研究发现：ox-LDL可诱导瓣膜内皮细胞钙化并促进细胞浆内Ca2+增加；钙化瓣膜组织中Calcineurin/NFATc1通路被激活，且相关报道证明NFATc1能够诱导内皮细胞炎症反应及成骨分化。因此，我们推测Calcineurin/NFATc1信号通路可能通过损伤瓣膜内皮，加重炎症细胞浸润，促进瓣膜间质细胞钙化等过程最终导致瓣膜钙化。本项目中拟构建DSCR-1 Tg转基因小鼠模型，结合Tanswell共培养，探讨Ca2+/Calcineurin/NFATc1轴激活、瓣膜内皮功能受损及瓣膜间质细胞钙化之间相互作用的机制，为主动脉瓣钙化发病机制提供新的理论依据，为临床防治提供新的靶点。

Ca2+/Calcineurin/NFATc1 axis participate and regulate various cardiovascular related diseases, but its role in Calcific aortic valve disease (CAVD) remains unclear. Our previous work found that ox-LDL induced the calcification of valve endothelial cells(VECs) and promoted the level of Ca2+ in cytoplasm; CAVD group had higher levels of Calcineurin/NFATc1 pathway than that in normal valves; NFATc1 induced the inflammatory and osteoblastic differentiation of ECs. We hypothesized that Ca2+ induced the VECs dysfunction, inflammatory response, osteoblastic differentiation and calcification of VICs, largely dependent on Calcineurin/NFATc1 pathway. To prove this hypothesis, this study will utilize ApoE and DSCR-1 transgenic mice, Transwell to investigate the role and the mechanisms of Ca2+/Calcineurin/NFATc1 axis in AV calcification pathogenesis. In vitro study, we will focus on the effect of Calcineurin/NFATc1 pathway on the dysfunction of VECs, VECs phenotype transition and its interaction with VICs. Our research will provide the first evidence on the pathogenesis of AV calcification and the theoretical and experimental basis for drug intervention of CAVD.