动脉粥样硬化是冠心病的主要病理基础，内质网应激在动脉粥样硬化中发挥重要作用。申请人前期研究发现一种应激活化的核糖核酸酶-血管生长素（ANG）在冠心病患者血浆中显著升高，而全身敲除ANG可加重ApoE-/-小鼠血管内质网应激并促进动脉粥样硬化形成。在肾损伤中，ANG通过tiRNA抑制eIF4F并促进应激颗粒形成而降低内质网应激，进而改善肾损伤。本项目从动脉粥样硬化内质网应激调控角度出发，提出“ANG是动脉粥样硬化中内质网应激重要调控分子”的科学假说，拟通过ApoE-/-小鼠和ANG-/-/ApoE-/-双基因敲除小鼠动脉粥样硬化和内皮细胞内质网应激模型及相关机制研究，探讨ANG通过tiRNA介导的eIF4F/应激颗粒途径抑制蛋白质翻译，降低内质网应激，进而改善血管内皮功能，阻断动脉粥样硬化进展。本研究将阐明ANG对内质网应激调控机制及其在动脉粥样硬化中的作用，为动脉粥样硬化防治提供新思路。

Atherosclerosis is the main pathological basis of coronary heart disease (CHD), and endoplasmic reticulum (ER) stress plays critical roles in the progression of atherosclerosis. We previously found that angiogenin (ANG), as a stress-activated ribonuclease, was elevated in CHD patients, while knockout of ANG aggravated vascular ER stress and promoted the progression of atherosclerosis in ApoE-/- mice. In kidney injury, ANG-mediated tiRNA reduced ER stress and improved kidney injury by inhibiting eIF4F and promoting stress granule assembly. It is reasonable to hypothesize that ANG might be an important regulator of ER stress in atherosclerosis. And in this project, ApoE-/- mice and ANG-/-/ApoE-/- mice models of atherosclerosis and HUVEC model of ER stress will be established to elucidate the regulating mechanisms of ANG-mediated tiRNA on ER stress through eIF4F/stress granule pathways and to illuminate the roles of ANG on endothelial dysfunction and atherosclerosis. Ultimately, we intend to provide a new idea for the prevention and treatment of atherosclerosis.