主动脉瓣病变中瓣膜钙化是导致瓣膜功能恶化的主要原因，但其具体机制目前尚不十分清楚。我们发现主动脉瓣膜在两种疾病状态：风湿性和退行性中均表现仅部分病人有瓣膜钙化，而BMP2拮抗剂SMOC-1基因在风湿性和退行性无钙化病变中显著高表达，提示SMOC-1基因可能是不同原因瓣膜钙化的一个共同环节。本研究将通过在不同病因来源的主动脉瓣间质细胞中研究SMOC-1对BMP2-Smad信号介导的成骨分化和钙化的调控作用，并在基因工程小鼠模型上验证体外细胞水平的研究结果，从而阐明SMOC-1的具体调控机制以及该机制是否是风湿性和退行性钙化所共有的。为临床寻找干预瓣膜钙化的分子靶点提供线索。

valvular calcification is the common condition leading to deterioration of valve function, the underlying mechanism remains largely unknown. Our previous study showed that only a part of the patients suffered from calcification either in rheumatic or in degenerative aortic valve disease. Nevertheless,BMP2 antagonist SMOC-1 was highly expressed both in rheumatic and degenerative non-calcific aortic valves, indicating that SMOC-1 may be the shared regulating path of differently etiological calcification.In this study, we will investigate how SMOC-1 regulates BMP2-Smad signaling induced osteoblastic differentiation and calcification of valvular interstitial cells obtained from rheumatic and degenerative aortic valve tissues with or without calcification. We will also study the effect of SMOC-1 on high-fat diet induced aortic valve disease in SMOC-1 transgenic and endothelial-knockout mice model，then to confirm the in vitro results. In conclusion, we will explore the detailed molecular regulation of BMP2-Smad singaling by SMOC-1 in rheumatic and degenerative aortic valve disease. We hope our study could provide some new insight for clinical treatment of aortic valvular calcification.