死亡受体4和5（DR4/5）是细胞因子TRAIL的细胞表面受体。和人类不同，小鼠只有DR5基因而没有DR4基因。在高脂血症的ApoE敲除小鼠中敲除其配体TRAIL后，动脉硬化斑块形成增加，因此TRAIL被认为具有血管保护作用。然而我们在前期研究中却意外发现，在ApoE敲除背景下，敲除DR5基因并没有复制TRAIL敲除后的血管表型，相反，ApoE/DR5双敲除后动脉粥样硬化形成减轻。为了揭示这种矛盾现象背后的生物学机制，本课题我们将利用我们自己建立的ApoE/DR5和LDLR/DR5双敲基因小鼠，系统研究DR5在调节血管炎症稳态及动脉粥样硬化形成中的角色和信号传导机制。我们的研究将阐明DR5受体是否是调节血管炎症稳态及动脉粥样硬化形成过程中关键的节点分子，为探索新的生物学靶点和干预措施提供理论基础。

Death receptors 4 and 5 (DR4/5) are the receptor of the cytokine TRAIL, a member of the tumour necrosis factor family. Mouse does not have DR4 gene, thus DR5 is the only TRAIL receptor in the mouse. TRAIL gene deletion increased atherosclerosis in hyperlipidemic ApoE-/- mice. However, in our preliminary study, we unexpectedly found that DR5 gene deletion in ApoE-/- mice did not pheno-copy that of TRAIL knockout, which indeed reduced atherogenesis. To clarify this paradoxical phenomenon, in this study we will use ApoE/DR5 and ApoE/LDLR double knockout mice created by our group and further clarify the role and underlying mechanisms of DR5 signaling in atherogenesis, and clarify whether DR5 represents a novel key regulator of the homeostasis of vascular inflammation.