钙化性主动脉瓣疾病（CAVD）高发且危害严重，亟需有效防治手段。牙周炎与多种心血管疾病密切相关。CAVD病变主动脉瓣可检出牙周炎病原福赛坦菌，但关系和机制未明。我们研究显示：①CAVD病变瓣膜可检出福赛坦菌DNA及其毒力蛋白BspA，伴胆固醇逆转运关键通路LXR-ABCA1水平降低；②ApoE-/-鼠口腔接种福赛坦菌使其更早出现主动脉瓣钙化；③BspA体外干预瓣膜间质细胞可抑制其LXR-ABCA1表达、增加钙化。由此假设：福赛坦菌侵袭主动脉瓣并下调瓣膜间质细胞LXR-ABCA1通路，致胆固醇流出减少、脂质沉积，诱发炎症并促进瓣膜钙化。本项目拟通过临床瓣膜标本检测，以野生型/突变型福赛坦菌和BspA体内干预小鼠模型、体外干预瓣膜间质细胞，观察LXR-ABCA1通路、脂质代谢、炎症反应和钙化改变，揭示福赛坦菌BspA下调LXR-ABCA1通路在CAVD形成中的作用机制，为其精准防控提供新思路。

Calcific aortic valve disease (CAVD) is an increasingly prevalent and extremely debilitating disease. Prevention and early intervention are critical but there is currently no effective medical treatment for this beyond surgical replacement. Periodontitis promotes the occurrence of cardiovascular diseases, periodontal pathogen - Tannerella forsythia can be detected in the calcified aortic valves from CAVD patients, but the connection between periodontitis and CAVD is unclear. We found that: ① from the calcified valves of CAVD, the DNA of Tannerella forsythia and its major virulence factor BspA can be detected; ② oral infection of Tannerella forsythia enhances the aortic stenosis in ApoE-/- mice model； ③ BspA recombinant protein downregulated the expression of LXR-ABCA1 in valvular interstitial cells, and promoted calcification in vitro. Thus, we hypothesize that Tannerella forsythia and its virulence factors BspA invasive the aortic valves and abnormalities in cholesterol metabolism and transportation by downregulating the LXR-ABCA1 pathway, which cause lipid deposition and inflammation in valve and improve CAVD. We intend to investigate the status of Tannerella forsythia invasion, LXR-ABCA1 pathway, lipid metabolism and deposition, inflammation and calcification in aortic valves. To further explore the cellular mechanisms， these changes will be confirmed in both mice model and in valvular interstitial cells，treated with Tannerella forsythia or its virulence factors. This study will shed new light on the strategy for the precise prevention and intervention of CAVD.