动脉钙化是临床上一项重要的心脑血管疾病预警指标，是动脉粥样硬化性疾病的重要病理机制之一，与VSMCs的成骨样表型转化密切相关。研究表明，lncRNA H19通过抑制NOTCH1信号通路促进成骨细胞分化，参与骨组织形成，但其在动脉钙化中的作用机制尚不明确。我们前期试验结果表明，动脉钙化患者lncRNA H19表达水平明显高于健康对照者。基于此，我们提出假说：lncRNA H19启动子区域低甲基化通过NOTCH1-HEY1-RUNX2信号通路促进VSMCs表型转化及动脉钙化的发生发展。本项目拟通过测量动脉钙化患者lncRNA H19启动子区域DNA甲基化水平，明确其与动脉钙化相关性；构建在体及离体钙化模型，采用siRNA干扰等技术，阐明H19启动子区域DNA甲基化通过NOTCH1信号通路在VSMCs表型转化及钙化发生发展中的分子机制。项目的实施将为临床防治动脉钙化导致的心血管事件提供新思路。

Arterial calcification(AC) is one of the most important clinical indicators of cardio-cerebrovascular disease(CCVD). It also plays a crucial role in the pathological mechanism of atherosclerotic diseases and closely associated with phenotypic transformation of VSMCs. Research has shown that long non-coding RNA H19 stimulates the differentiation of osteoblasts by inhibiting NOTCH1 signal pathway and participate in osteogenesis,however the mechanism of H19 in arterial calcification is not clear. Preliminary result of our earlier research shows a higher level of lncRNA H19 in patients with arterial calcification compared with individuals without AC . In light of this, we hypothesize that “Dysregulation of DNA methylation in the promoter region of H19 during AC promotes the phenotypic transformation of VSMCs and initiates osteogenic process by NOTCH1-HEY1-RUNX2 pathway”. Our project is to measure the DNA methylation in the promoter region of H19 in AC patients to determine the correlation between H19 and AC, construct AC model in vivo and in vitro,using siRNA technology, to illuminate the mechanism of the DNA methylation in the promoter region of H19 to promote the phenotypic transformation of VSMCs and osteogenic process by NOTCH1 pathway. The implementation of the projects will provide new ideas for prophylaxis and treatment of adverse cardiovascular events mediated by AC.