二叶式主动脉瓣（BAV）钙化狭窄是临床最为常见且严重的心脏瓣膜疾病。研究表明BAV钙化过程与瓣膜间质细胞（VIC）中成骨基因表达调控出现异常有密切关系。我们对钙化性BAV患者标本行芯片筛查发现LncRNA UCA1参与VIC钙化的调控、与钙化相关因子SMAD7的异常表达有关；且发现VIC中SMAD7的表达受miRNA-195负向调控。但目前尚不明确BAV钙化进程中LncRNA UCA1与miRNA-195是否通过竞争性结合，共同调控SMAD7的表达。我们将运用非编码RNA转录后调控检测技术和基因诊断技术，研究BAV钙化病理过程的重要原因，揭示LncRNA UCA1在钙化性BAV病变中的关键作用。本项目将有助于阐明非编码RNA精准调控BAV钙化的新机制（ceRNA机制），为基因治疗BAV钙化提供新的线索和干预靶标。

Bicuspid aortic valve (BAV) calcification and stenosis is the most common and serious heart valve disease. Studies have shown that BAV calcification is closely related to the abnormal regulation of osteogenic gene expression in valve interstitial cells (VIC). Our microarray screening of calcified BAV patients revealed that LncRNA UCA1 is involved in the regulation of VIC calcification and is associated with the abnormal expression of calcification-related factor SMAD7. It was also found that the expression of SMAD7 in VIC was negatively regulated by miRNA-195. However, it is not clear whether LncRNA UCA1 and miRNA-195 compete for binding in the process of BAV calcification to jointly regulate the expression of SMAD7. We will use non-coding RNA post-transcriptional regulatory techniques and gene diagnostic techniques to study the important causes of pathological changes in BAV calcification and to reveal the key role of LncRNA UCA1 in calcified BAV lesions. This project will help elucidate the novel mechanism (ceRNA mechanism) for non-coding RNA to precisely regulate BAV calcification, and provide new clues and intervention targets for gene therapy for BAV calcification.