快速发展的动脉粥样硬化是类风湿关节炎（RA）患者罹患心血管病的首要死亡原因。传统心血管病危险因素不能完全解释这一现象，其可能与RA患者长期慢性全身性炎症反应有关，但RA体内慢性炎症与血管内皮损伤的机制尚未明确。干扰素λ1是一种新型细胞因子，我们在上一个国家自然基金资助下首次证实IFN-λ1在RA中具有重要促炎作用。结合预实验结果IFN-λ1在血管内皮细胞异常表达，我们推测IFN-λ1可能通过其介导的全身和局部炎症反应参与血管内皮损伤，是连接RA慢性炎症和内皮细胞受损的重要桥梁。本课题拟从动物、组织、细胞和分子水平，以滑膜细胞和主动脉内皮细胞为切入点，利用过表达、RNA干扰、构建稳转细胞株、芯片检测等技术系统研究IFN-λ1在RA血管内皮损伤中的作用及调控机制。研究结果将为揭示RA血管内皮损伤发生和发展的机制奠定基础，为RA合并动脉粥样硬化的防治提供新思路。

Rapid development of atherosclerosis is the number cause of death in rheumatoid arthritis (RA) patients, which can not be fully explained by the traditional and non-traditional cardiovascular risk factors.Previous studies have demonstrated that chronic and systemic inflammation in RA is associated with defective endothelium, but the mechanism is unclear.Our preliminary studies have shown that interferon-lambda1 (IFN-lambda1), a newly identified cytokine, is an important pro-inflammatory cytokine in RA. Because of its elevated expression in RA endothelial cells, we hypothesize that a high level of INF-lambda1 causes endothelial injuries and promotes RA atherosclerosis through local and systemic inflammation to release pro-inflammatory factors in RA， which may link RA with impaired endothelial dysfunction.This project will test this hypothesis from animal,tissue,cellular and molecular levels,using combination of over-expression, RNAi,transfection, microarray approaches, especially focused on synovial cells and aortic endothelial cells，to study and reveal in vivo and in vitro the underlying mechanisms by which INF-lambda1 induces endothelial injuries and promotes RA atherosclerosis. Completion of this project will elucidate the roles of chronic inflammation in the pathogenesis of RA atherosclerosis and provide new strategies to prevent or treat RA atherosclerosis.