钙化性主动脉瓣膜疾病 (CAVD) 严重影响老年人的生活质量，而临床上缺乏有效的治疗药物。Lp(a) 是一个独立的促进瓣膜钙化因素，但具体机制尚不清楚。骨形态发生蛋白 (BMPs) 是促成骨钙化的重要分子。我们前期研究证实，在体外实验中Lp(a) 可以促进 BMP-7 表达；钙化的 CVAD 组织中 BMP-7 表达升高；BMP-7 可以诱导瓣膜间质细胞向成骨钙化方向分化；生物信息学分析到 BMP-7 下游重要的信号分子 Runx2 可以结合到编码 Lp(a) 特异性蛋白的基因 (LPA) 启动子上。因此，我们将借助一系列手段研究 BMP-7 通过哪些分子机制导致 VIC 钙化；Lp(a) 如何诱导 BMP-7 表达上调，Runx2 是否结合 LPA，从而形成一条 Lp(a), BMP-7, Runx2, Lp(a) 环路。该项目的实施将进一步完善人们对 CAVD 的认识。

Calcific aortic valve disease (CAVD) seriously affect elderly, but lack effective treatment at present. Lipoprotein a [Lp(a)] is an independent factor in the promotion of valvular calcification, but the specific mechanism is unclear. Bone morphogenetic proteins (BMPs) are important elements to promote bone calcification. Our previous study showed that BMP-7 is promoted by Lp(a) in vitro. There is high level of BMP-7 in CAVD. VIC could be induced into osteogenesis calcification differentiation by BMP-7. One of the most important downstream factor of BMP-7, Runx2, could bind to LPA promoter which encode specific particle of Lp(a). With a series of research methods, we will research what mechanism that BMP-7 induced VIC calcification. How BMP-7 was promoted by Lp(a). Whether Runx2 binding to LPA or not. Thereby a Lp (a) - BMP-7 - Runx2 - Lp (a) loop is formed. The implementation of the project will further improve the people's understanding about heart valve calcification specific mechanism.