CapG蛋白通过调控巨噬细胞功能参与动脉粥样硬化发生发展的机制研究

Atherosclerosis is a progressive disease with different stages, and many different molecules are involved in different processes including plaque formation, progression and destabilization. The proteome atlas of each stage was still not reported until now, and the comprehensive dynamic alterations of molecules involving atherosclerosis have not been illustrated. We performed a deeply comprehensive proteomics profiling using human diseased coronary artery with different stages of atherosclerosis dissected from the same explanted heart, in order to illustrate the dynamic alterations of proteins. Our primary proteome study revealed that CapG protein was significantly increased during atherosclerosis progression especially at plaque destabilization process. Previous studies demonstrated that CapG was associated with migration and phagocytosis function of macrophage, but no studies directly illuminate the role of CapG in atherosclerosis. And thus, we put forward the hypothesis that CapG protein involves in destabilization of atherosclerosis plaque through regulating migration and phagocytosis function of macrophage. This project will perform in-vitro study based on human and murine derived macrophage and ApoE-/- atherosclerosis murine model to study the role of CapG protein in progression of atherosclerosis.

冠状动脉粥样硬化是一种动态的冠脉病变进展过程。目前国际上尚无绘制冠脉粥样硬化各个病变进展时期蛋白质组学动态改变的报道。前期通过对因终末期冠心病行心脏移植受体心脏冠脉解剖，获取同一心脏5个不同病变时期（正常，内膜增厚，稳定斑块，不稳定斑块及破裂斑块）冠状动脉，利用深度定量蛋白质组学分析揭示各个病理时期蛋白图谱。我们发现：CapG蛋白在斑块的不稳定发展过程中显著升高，由于CapG蛋白与巨噬细胞迁移及吞噬功能密切相关，基于前期工作及现有理论提出假设：CapG蛋白通过调节巨噬细胞的迁移与吞噬功能，参与动脉粥样硬化斑块不稳定化过程。本研究拟利用体外巨噬细胞模型及ApoE-/-动脉粥样硬化小鼠模型研究CapG蛋白在动脉粥样硬化疾病进展发生机制，为冠心病治疗早期干预提供靶点。

冠状动脉粥样硬化是一种动态的冠脉病变进展过程。目前国际上尚无绘制冠脉粥样硬化各个病变进展时期蛋白质组学动态改变的报道。前期通过对因终末期冠心病行心脏移植受体心脏冠脉解剖，获取同一心脏5个不同病变时期（正常，内膜增厚，稳定斑块，不稳定斑块及破裂斑块）冠状动脉，利用深度定量蛋白质组学分析揭示各个病理时期蛋白图谱。深入分析发现与斑块不同性质相关的蛋白类型为解析冠脉连续性病变奠定了基础。随后通过对不同斑块进行飞行靶向质谱成像探究，阐明不同阶段的冠脉粥样硬化代谢组特征，寻找预测粥样硬化进展特异性代谢物，为未来进行干预实验提供了重要的基础。最后深入细胞层面研究冠脉病变特征，首先通过病理检查筛选正常的血管进行单细胞测序，构建了心脏血管的细胞构成图谱，随后对收集不同病变的冠脉样本进行单细胞测序，目前初步完成测序阶段，未来将进行进一步深入分析过程。通过本研究课题探究，我们从蛋白层面、代谢层面、单细胞层面全方位立体地揭示动脉粥样硬化疾病进展发生机制，为冠心病治疗早期干预提供靶点。