hsa_circ_0016274调控MMP9介导细胞自噬在急性冠脉综合征斑块易损性中的作用及分子机制探究

冠心病的主要死因是冠脉内粥样硬化斑块破裂诱发的急性冠脉综合征(ACS)。既往研究已证实细胞自噬和基质金属蛋白酶9(MMP9)均可影响斑块易损性。我们前期发现hsa_circ_0016274作为去泛素化酶(YOD1)的剪切体能调节细胞自噬和MMP9表达从而增加斑块易损性，基于此，我们假设：1、hsa_circ_0016274可增加IκB泛素化降解而激活NF-κB通路，并能与miR-296-3p竞争结合靶基因，上调MMP9表达；2、hsa_circ_0016274/miR-296-3p能通过Akt/mTOR通路减少细胞自噬；从而导致稳定斑块破裂。本研究拟构建高脂血症动脉粥样硬化模型小鼠及细胞模型、过表达及敲低靶基因技术，检测相关炎性因子及蛋白表达的变化。探讨hsa_circ_0016274在ACS发病中的作用及分子机制，为探索新的ACS防治手段提供新的理论基础和实验依据。

The main cause of death of coronary artery disease (CAD) is acute coronary syndrome (ACS) incident by the rupture of atherosclerotic plaque. It has been confirmed that autophagy and matrix metalloproteinase 9 (MMP9) can affect plaque vulnerability. We have previously found that hsa_circ_0016274, as a part of the ubiquitinase (YOD1), which can regulate the expression of autophagy and MMP9, and increase the vulnerability of plaque. Based on that, we speculated that: 1. hsa_circ_0016274 not only increase the ubiquitin degradation of IκB and activate NF - κB pathway, but also can it compete with miR-296-3p to bind to the target gene, and up regulate the expression of MMP9; 2. hsa_circ_0016274/miR-296-3p can affect Akt/mTOR pathway to reduce autophagy, which lead to stable plaque ruptured. The aim of this study is to construct the atherosclerosis mice model and cell model, overexpression and knockdown target gene, and detect the changes of related inflammatory factors and protein expression. To explore the role and molecular mechanism of hsa_circ_0016274 in the pathogenesis of ACS, and to provide a new theoretical basis and experimental basis for the exploration of new methods of prevention and treatment of ACS.