内皮屏障破坏及单核细胞内皮下浸润是动脉粥样硬化（AS）发生发展的关键。AS是血管炎症性疾病，泡沫细胞是维持血管局部非可控炎症并促AS进展的关键细胞。内皮细胞在炎症等因素作用下内皮表型消失，代以间质细胞表型，发生内皮间质转化（EndMT）而使内皮屏障受损。我们发现泡沫细胞上清可诱导内皮细胞发生间质转化，高脂喂养的Ldlr-/-小鼠AS斑块表面内皮亦存在EndMT，并与AS进程相关。通过泡沫细胞和AS斑块的炎症因子基因芯片共分析发现包括趋化因子CCL20在内的多种炎症相关因子高表达，抑制CCL20可减轻泡沫细胞上清诱导的EndMT。故推测泡沫细胞通过旁分泌CCL20作用于内皮趋化因子受体CCR6使其发生EndMT而致内皮屏障受损，促AS进展。本项目拟以Ldlr-/-小鼠高脂饮食致AS模型观察EndMT、CCL20与AS的关系，并探讨其机制，为深入认识AS进展提供新思路，并为AS防治提供新靶点。

Endothelial barrier disruption and monocytes infiltrating into subendothelial are the key factors for atherogenesis and its development. Atherosclerosis (AS) as the vascular imflammatory disease, foam cells play a pivotal role in its development and the maintenance of local vessel nonresolving inflammation. Endothelial cell will lose the endothelial phenotypes and be replaced by interstitial cells’ phenotypes, which is called as endothelial-mesenchymal transition (EndMT) when stimulated by inflammation or other stimulation. EndMT can result in endothelial barrier disruption, and be beneficial for monocytes infiltrating into subendothelium. We have found that the supernatant from cultured foam cells could induce EndMT in endothelial cells, and EndMT could also found in the surface of atherosclerotic plaque in high fat-fed Ldlr-/- mice. In addition, the EndMT was related to the development of AS. We further performed the gene chip analysis of inflammatory factors in foam cells and atherosclerotic plaque. It was found that many inflammatory factors including chemokine CCL20 had very high expression, and inhibiting CCL20 could attenuate the EndMT induced by foam cell supernatant. So we speculated that foam cell could promote EndMT and subsequent endothelial barrier dysfunction, and promote AS development by producing paracrine factor CCL20. Accordingly, the present project aimed to determine the relation among EndMT, CCL20, and AS and the possible mechanisms in Ldlr-/- AS mice induced by high-fat diet, which would help to further explore the new mechanism of AS and search new therapeutic target point for the prevention and treatment of AS.