动脉中膜钙化是血管壁发生的一种类似骨形成的主动调节过程，血管平滑肌细胞（VSMCs）向成骨样细胞转分化是其细胞学基础。既往研究仅关注VSMCs的转分化，而内皮细胞和VSMCs构成血管壁微环境，内皮细胞调控VSMCs的转分化研究较少。我们前期研究发现尿毒症血清可促进内皮细胞分泌富含miR-27b的外泌体，该外泌体被VSMCs摄取后，促进VSMCs向成骨样细胞分化。本项目探讨尿毒症血清干预内皮细胞来源富含miR-27b的外泌体被VSMCs摄取后，调控VSMCs向成骨样细胞分化的分子机制。通过在动脉中膜钙化动物模型及临床标本中证实miR-27b与动脉中膜钙化的关系，并采用内皮细胞特异性敲除miR-27b小鼠，观察尿毒症加高磷饮食对动脉中膜钙化的影响。本项目从血管壁微环境出发，探讨内皮细胞调控VSMCs向成骨样细胞分化的分子机制，揭示动脉中膜钙化新的发病机制，为动脉中膜钙化防治提供新的作用靶点。

Arterial medial calcification is a positive regulation process resembling bone formation in arterial wall, and the osteoblastic transdifferentiation of vsascular smooth muscle cells (VSMCs) is the cytologic mechanism of arterial medial calcification. Previous study only focus on the transdifferentiation of VSMCs, however, endothelial cell and VSMCs constitute the microenvirment of arterial wall, and there is little information about the endothelial cell regulting the osteoblastic transdifferentiation of VSMCs. Our previous studies demonstrate exosome free uremia serum could stimulate the secretion of exosome enrichment with miR-27b in endothelial cell. The exosome could be uptaken by the VSMCs, resulting in accelerating osteoblastic transdifferentiation of VSMCs. Our present study investigate the molecular mechanism involved in enrichment miR-27b exosome regulting osteoblastic transdifferentiation of VSMCs after these exosome uptaken by VSMCs. Using arterial medical calcification mice model and clinical arterial medial calcification sample, the relationship between miR-27b and arterial medial calcification will be investigated. Using Endothelial cell-specific miR-27b knockout mice, the effect of endothelia cell original miR-27b on arterial medial calcification will be analysised. The project devote to reveal the new mechanism of arterial calcification based on the arterial wall microenvirment. The project will find a new target for treatment of arterial medial calcification.