类风湿关节炎（RA）是一种高发病率的致残性疾病，常伴心血管并发症，研究RA及其心血管并发症的机制和治疗措施具有重大意义。炎症状态下，炎症细胞通过NF-κB及MAPKs通路促进成纤维样滑膜细胞及破骨细胞活化，导致骨质破坏；同时炎症活化心肌成纤维细胞，导致心室重构。既往研究证实ACE2/Ang-(1-7)/Mas轴参与抗炎、抗纤维化及脂质代谢，但在RA及心血管并发症中的研究国内外尚无报道。本项目旨在前期工作基础上(NSFC81200519）首次利用炎症状态下培养的成纤维样滑膜细胞、心肌成纤维细胞、巨噬细胞及小鼠关节炎模型，探讨ACE2/Ang-(1-7)/Mas轴通过抑制NF-κB及MAPKs通路，减少炎症因子释放，抑制破骨细胞活化，起到减轻关节骨质破坏的作用；并探讨该轴对炎症状态下心血管的保护作用，从而明确该轴干预关节炎症及心血管并发症的机制与地位，为临床寻找RA新的治疗途径提供理论依据。

Rheumatoid arthritis (RA) is a crippling disease with high morbidity and common cardiovascular complication. Therefore it is of great significance to investigate the mechanism of RA complicated with cardiovascular disease and to explore effective therapeutic measures for it. In the inflammatory state, inflammatory cells promote the activation of fibroblast-like synoviocytes and osteoclasts via NF-κB and MAPKs inflammatory signaling pathway to cause bone destruction. In addition, activation of cardiac fibroblasts in inflammatory state leads to ventricular remodeling. Previous studies have indicated that the ACE2/Ang-(1-7)/Mas axis participates in the anti-inflammatory and anti-profibrotic actions, as well as lipid metabolism. However, the role of this axis in RA complicated with cardiovascular disease is unclear at present. Based on our previous work (NSFC: 81200519）, this project aims, for the first time, to investigate the inhibitory effect of ACE2/Ang-(1-7)/Mas axis on the destruction of articular bone by inhibiting NF-κB and MAPKs inflammatory signaling pathway to reduce the release of inflammatory factor and restrain the activation of osteoclasts in cultured fibroblast-like synoviocytes, cardiac fibroblasts and macrophages under inflammatory condition and in arthritis mouse models. Moreover, this project will investigate the protective effect of ACE2/Ang-(1-7) /Mas axis on cardiovascular system under arthritis condition to elucidate the mechanism and role of the ACE2/Ang-(1-7)/Mas axis in intervening both arthritis and complicated cardiovascular disease, which can provide a theoretical basis for a new therapy for RA in clinic.