动脉粥样硬化（AS）斑块稳定性是决定冠心病患者预后的重要因素，炎症在AS进展及易损斑块形成中发挥重要的作用。作为斑块最主要的成分，平滑肌细胞（VSMCs）功能状态与炎症反应密切相关。我们前期研究发现进展期斑块内存在大量程序性坏死的VSMCs，程序性坏死的细胞引起并加重炎症反应，我们推测程序性坏死的VSMCs是AS发展及易损斑块形成的关键促进因素，调控平滑肌细胞程序性坏死可能是治疗AS的新方向，但目前尚无相关研究。ROS是抑制细胞程序性坏死的重要靶点。我们前期工作证明抗炎性脂肪因子CTRP9可促进抗氧化酶表达，抑制ROS，可能具有调控VSMCs程序性坏死的作用。本项目拟通过构建转基因模式动物，探索VSMCs程序性坏死在AS中的作用，并证实CTRP9可通过调控VSMCs程序性坏死抑制AS。本项目对于明确VSMCs程序性坏死是否可作为AS新的干预靶点及CTRP9对于AS的治疗作用具有重要的意义。

Atherosclerosis (AS) plaque stability is an important prognostic factor in patients with coronary heart disease, inflammation plays an important role in AS progression and vulnerable plaque formation. As the most important component of AS plaque, the functional status of smooth muscle cells (VSMCs) is closely related to inflammation. Previous studies have found that there are a large number of necroptosis VSMCs in advanced plaques, which cause and aggravate inflammation. We speculate that necroptosis VSMCs are the key factors to promote the development of AS and the formation of vulnerable plaques, and regulating the necroptosis of VSMCs may be a new direction in the treatment of AS, but there is no relevant research at present. ROS is an important target for inhibiting necroptosis. Our previous work has proved that anti-inflammatory adipokine CTRP9 can promote the expression of antioxidant enzymes and inhibit ROS, which may play a role in regulating the necroptosis VSMCs. This project aims to explore the role of necroptosis VSMCs in AS via establishing transgenic model animals, and confirm that CTRP9 can repress AS through regulating necroptosis VSMCs, also it is of great significance to clarify whether necroptosis VSMCs can be used as a new intervention target for AS and the therapeutic effect of CTRP9 on AS.