Interactive Signaling Modules in Vascular Remodeling

项目申请“血管重构中的交互信号模块”由康涅狄格大学法明顿健康中心血管活检中心提出。该项目由四个项目和五个核心组成，重点研究血管重塑的过程。该项目汇集了7位对血管重塑过程感兴趣的独立研究者。该计划的主题是定义重要的生理和病理血管重塑过程的分子机制。该计划的主题是定义重要的生理和病理血管重塑的分子机制。核心假设是不同的信号转导通路相互作用，调节基本的细胞过程，如细胞迁移、增殖、分化、死亡和细胞间相互作用，最终导致脉管系统结构的改变。该计划中的每个项目都侧重于主题的一个独特方面，以提高我们对血管重塑的理解。项目1 （H1a）提出研究血小板源性溶血磷脂介质鞘氨醇1-磷酸（S1P）的生理基础。S1P信号通过EDG家族的g蛋白偶联受体调节内皮细胞迁移、内皮细胞/周细胞相互作用和血管成熟将被研究。该项目与项目2 （Fong）有几个共同的兴趣，项目2的重点是缺氧如何影响胚胎中新生脉管系统的形态发生。HIF-2alpha是一种缺氧敏感的转录因子，将被研究以了解调节血管重构的信号通路。项目3 （Wu/Claffey）研究病理性血管重构；在体外和体内研究pi -3-激酶- γ、PLCbeta2/3通路在调节g蛋白依赖性单核细胞活化和趋化中的具体作用。这个项目与项目1和项目4有着相当多的共同目标。Project 4 （Han）关注的是细胞-细胞识别过程，通过该过程凋亡细胞从血管壁上被清除。因此，本项目与项目3和项目1有共同的兴趣，并涉及病理性血管重构问题。所有项目均采用分子、生化、细胞生物学和体内模型。因此，提出了五个核心，即行政管理核心，荧光成像核心，组织学核心，蛋白质组学核心和基因操作核心，以支持最先进的技术项目。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，预计该项目申请将对血管重塑产生重大的新见解。

The program project application "Interactive signaling modules in vascular remodeling" is proposed from the Center for Vascular Biopsy at the University of Connecticut Health Center, Farmington. This program is composed of four projects and five cores and is focused on the process of vascular remodeling. The program brings together seven independent investigators interested in the vascular remodeling processes. The theme of the program is to define molecular mechanisms important for physiologic and pathologic vascular remodeling processes. The theme of the program is to define molecular mechanisms important for physiologic and pathologic vascular remodeling. The central hypothesis is that distinct signal transduction pathways interact with each other to modulate fundamental cellular processes such as cell migration, proliferation, differentiation, death and cell-cell interaction, ultimately leading to alterations in the structure of the vasculature. Each project in the program focuses on a unique aspect of the theme to advanced our understanding of vascular remodeling. Project 1 (H1a) proposes to investigate the physiological basis of the platelet-derived lysophospholipid mediator, sphingosine 1-phosphate (S1P). Signaling of S1P via the G-protein- coupled receptors of the EDG family to regulate endothelial cell migration, endothelial cell/pericyte interactions and vascular maturation will be investigated. This project shares several common interests with Project 2 (Fong), which is focused on how hypoxia affects vascular endothelial cells during the morphogenesis of the nascent vasculature in the embryo. A hypoxia-sensitive transcription factor, HIF-2alpha will then be investigated to understand signaling pathways that regulate vascular remodeling. Project 3 (Wu/Claffey) addresses pathological vascular remodeling; the specific role of PI-3-kinase-gamma, PLCbeta2/3 pathways, which modulate G-protein-dependent monocyte activation and chemotaxis will be investigated in vitro and in vivo. This project shares considerable common goals as projects 1 and 4. Project 4 (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 3 and 1 and deals with the issue of pathologic vascular remodeling. All the projects utilizes molecular, biochemical, cell biological and in vivo models. Thus five cores, administrative, fluorescence imaging, histology, proteomics and gene manipulation cores, are proposed to support the projects in 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 remodeling will be forthcoming from this program project application.