Interactive Signaling Modules in Vascular Inflammation

竞争性更新项目应用“血管炎症中的交互信号模块”，重点研究血管壁炎症变化导致动脉粥样硬化的过程。该项目汇集了7位对血管生物学感兴趣的独立研究者。该计划的主题是定义病理性炎症事件的重要分子机制，重点是骨髓细胞。核心假设是不同信号转导模块之间的相互作用影响基本的细胞过程，如细胞间相互作用、细胞迁移、炎症、死亡和凋亡细胞的吞噬，最终改变动脉粥样硬化的发病机制和进展。该计划中的每个项目都侧重于主题的一个独特方面，以促进我们对炎症血管表型的理解。Project 1 （Hla）提出研究鞘氨醇1-磷酸在巨噬细胞炎性体功能和动脉粥样硬化中的作用。该项目与项目2 （Wu）有几个共同的兴趣，项目2的重点是PLCB调控巨噬细胞凋亡和动脉粥样硬化。项目3 （Han）关注细胞-细胞识别过程，通过该过程凋亡细胞从血管壁上清除。因此，该项目与项目2和项目4具有共同的兴趣。Project 4 （Shapiro）专注于细胞表面分子CD13在髓细胞粘附血管内皮细胞中的新作用，并探讨了这种血管病理机制。所有项目均采用分子、生化、细胞生物学和活体小鼠模型。因此，三个核心，行政，荧光成像和血管组织学和动脉粥样硬化提出了最先进的技术来支持项目。所有的项目和核心相互作用，相互促进，以协同的方式实现项目的目标。再加上对血管生物学中心强有力的机构支持，预计这项更新计划的项目申请将对血管炎症和动脉粥样硬化产生重大的新见解。相关性（见说明）：血管壁炎症对动脉粥样硬化很重要，动脉粥样硬化会导致心脏病发作。血液单核细胞进入血管壁，分化为巨噬细胞并维持炎症。本项目将重点研究单核细胞进入的新机制、巨噬细胞炎症机制、巨噬细胞存活和吞噬死亡或凋亡细胞。这些合作研究将有助于更好地了解动脉粥样硬化，并为控制动脉粥样硬化提供潜在的新治疗方向。

The competitive renewal of the program project application "Interactive signaling modules in vascular inflammation" is focused on the process of inflammatory changes in the vessel wall that lead to atherosclerosis. The program brings together seven independent investigators interested in the vascular biology. The theme of the program is to define molecular mechanisms important for pathologic inflammatory events with a focus on myeloid cells. The central hypothesis is that interactions between distinct signal transduction modules influence fundamental cellular processes such as cell-cell interaction, cell migration, inflammation, death and engulfment of apoptotic cells, ultimately altering the pathogenesis and progression of atherosclerosis. Each project in the program focuses on a unique aspect of the theme to advance our understanding of inflammatory vascular phenotypes. Project 1 (Hla) proposes to investigate the role of sphingosine 1-phosphate on macrophage inflammasome function and atherogenesis. This project shares several common interests with Project 2 (Wu), which is focused on PLCB regulation of macrophage apoptosis and atherogenesis. Project 3 (Han) focuses on the process of cell-cell recognition process by which apoptotic cells are cleared from the vascular wall. Thus, this project has common interests as projects 2 and 4. Project 4 (Shapiro) focuses on the novel role of the cell-surface molecule CD13 in the adhesion of myeloid cells to vascular endothelial cells, and explores this mechanism in vascular pathology. All the projects utilize molecular, biochemical, cell biological and in vivo mouse models. Thus three cores, administrative, fluorescence imaging and vascular histology and atherosclerosis are proposed to support the projects with state-of-the-art technology. All the projects and cores interact and mutually reinforce each other to achieve the goals of the program in a synergistic manner. Coupled with strong institutional support to the Center for Vascular Biology, it is anticipated that significant new insights on vascular inflammation and atherosclerosis will be forthcoming from this renewal program project application. RELEVANCE (See instructions): Inflammation in the vessel wall is important in atherosclerosis, which leads to heart attacks. Blood monocytes enter the vessel wall, differentiate into macrophages and sustain inflammation. This project will focus on new mechanisms of monocyte entry, macrophage inflammatory mechanisms, macrophage survival and engulfment of dead or apoptotic cells. These collaborative studies should lead to better understanding of atherosclerosis and provide potential new therapeutic directions to control atherosclerosis.