Interactive Signaling Modules in Vascular Inflammation

该计划项目应用程序的竞争性更新“血管炎症中的交互式信号传导模块”专注于导致动脉粥样硬化的血管壁炎症变化的过程。该计划汇集了七名对血管生物学感兴趣的独立研究人员。该计划的主题是确定重要的病理炎症事件的分子机制，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-细胞相互作用、细胞迁移、炎症、凋亡细胞的死亡和吞噬，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。项目1（Hla）提出研究1-磷酸鞘氨醇对巨噬细胞炎性体功能和动脉粥样硬化形成的作用。该项目与项目2（Wu）有几个共同的兴趣，项目2的重点是PLCB对巨噬细胞凋亡和动脉粥样硬化形成的调节。项目3（Han）关注细胞-细胞识别过程，通过该过程，凋亡细胞从血管壁中清除。因此，该项目与项目2和项目4具有共同利益。项目4（Shapiro）重点关注细胞表面分子CD 13在骨髓细胞与血管内皮细胞粘附中的新作用，并探索血管病理学中的这种机制。所有项目都利用分子、生物化学、细胞生物学和体内小鼠模型。因此，提出了三个核心，行政，荧光成像和血管组织学和动脉粥样硬化，以支持国家的最先进的技术项目。所有的项目和核心相互作用，相互加强，以协同的方式实现计划的目标。再加上对血管生物学中心的强有力的机构支持，预计这一更新计划项目申请将带来对血管炎症和动脉粥样硬化的重要新见解。相关性（见说明）：血管壁的炎症在动脉粥样硬化中很重要，动脉粥样硬化导致心脏病发作。血液单核细胞进入血管壁，分化成巨噬细胞并维持炎症。这个项目将集中在单核细胞进入，巨噬细胞炎症机制，巨噬细胞存活和吞噬死亡或凋亡细胞的新机制。这些合作研究应该导致更好地了解动脉粥样硬化，并提供潜在的新的治疗方向，以控制动脉粥样硬化。

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.