动脉粥样硬化(As)在本质上属于慢性炎症性疾病，内皮的损伤和功能紊乱是其发生的关键和必须因素，血管平滑肌细胞的增殖和迁移与As形成密切相关。研究显示重度慢性牙周炎与As高度相关，牙周炎所致菌血症可使其致病菌P.gingivalis进入血液循环，损伤/激活内皮细胞、影响平滑肌细胞功能。但这是否牙周炎与As相关的生物学基础与机制以及其中的分子病理过程尚不清楚。本研究拟分析致病毒力不同的不同fimA基因型P.gingivalis及其毒力因子对模拟血管环境共培养条件下内皮和平滑肌细胞功能的影响而导致As发生发展的可能，并通过动物实验分析P.gingivalis激活内皮细胞天然免疫信号转导相关受体、转录因子和调节机制以及对平滑肌细胞增殖和迁移的影响，探讨P.gingivalis在As发生发展中的可能作用和机制及其在牙周炎与As相关性中的意义，为As的早期防治提供新思路。

Atherosclerosis (As) is a chronic inflammatory disease in essence. Endothelial injury and dysfunction is the critical factor that triggers the onset of atherosclerosis. Proliferation and migration to the endothelial layer of vascular smooth muscle cells (SMCs) is closely related to the formation of atherosclerotic lesion. Studies have strongly indicated that severe chronic periodontitis correlated with atherosclerosis and atherosclerotic cardiovascular diseases. Bacteremia resulted from occlusion, tooth-brushing, and dental treatment in patients with severe periodontitis may allow the periodontal pathogen P.gingivalis to enter into systemic circulation and gain access to vasculature. Furthermore, P.gingivalis has been demonstrated to invade into and activate vascular endothelial cells (VECs) and influence the function of VECs and SMCs. However, it remains unclear how P.gingivalis is involved in the development of atherosclerosis and what is the nature of the molecular mechanisms underlying the relationship between periodontitis and atherosclerosis. This study will try to analyze the effects of P.gingivalis with different fimA genotypes which possessing different pathogenic virulence and the bacterial cell surface components on the functions of VECs and SMCs co-cultured in floating collagen gel co-culture system which to mimic the blood vessel condition in vitro, and with animal models, to analyze the biological mechanisms involved in the initiation of P.gingivalis-accelerate atherosclerosis and the related surface receptors and transcriptional factors of VECs that utilized by P.gingivalis in the innate immune signaling pathway of activation of VECs and the effects of P.gingivalis on the proliferation and migration of SMCs in vivo. Based on the above studies, we will try to explore the roles and significance of P.gingivalis infection in the pathogenesis and progression of atherosclerosis and the biological mechanisms which link P.gingivalis, peiodontitis, and developement of atherosclerosis, to provide some new considerations and approaches for prevention and control of atherosclerosis.