Interactive Signaling Modules in Vascular Remodeling

项目应用“血管重塑中的交互信号模块”是由位于法明顿的康涅狄格大学健康中心血管活检中心提出的。该计划由四个项目和五个核心组成，重点关注血管重塑的过程。该项目汇集了七名对血管重塑过程感兴趣的独立研究人员。该计划的主题是确定对生理性和病理性血管重塑过程重要的分子机制。该项目的主题是确定生理性和病理性血管重塑的重要分子机制。中心假设是不同的信号转导途径相互作用，调节基本的细胞过程，如细胞迁移、增殖、分化、死亡和细胞-细胞相互作用，最终导致血管系统结构的改变。该计划中的每个项目都集中在主题的一个独特方面，以促进我们对血管重塑的理解。项目1(H1a)建议研究血小板衍生的溶血磷脂介体--1-磷酸鞘氨醇(S1P)的生理基础。将研究S1P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的信号。这个项目与项目2(FONG)有几个共同的兴趣，后者专注于低氧如何在胚胎新生血管系统的形态发生过程中影响血管内皮细胞。然后，我们将研究缺氧敏感的转录因子HIF-2pha，以了解调节血管重构的信号通路。项目3(Wu/Claffey)致力于病理性血管重塑；将在体外和体内研究调节G蛋白依赖的单核细胞激活和趋化的PI-3-激酶-伽马、PLCbeta2/3通路的具体作用。这个项目与项目1和项目4有相当大的共同目标。项目4(HAN)专注于细胞-细胞识别过程，通过细胞识别过程将凋亡细胞从血管壁中清除。因此，这个项目与项目3和项目1有共同的兴趣，并处理病理性血管重构的问题。所有项目都利用了分子、生化、细胞生物学和活体模型。因此，提出了五个核心，即行政、荧光成像、组织学、蛋白质组学和基因操作核心，以支持最先进技术的项目。所有项目和核心相互作用，相互加强，以协同的方式实现方案的目标。再加上对血管生物学中心的强有力的机构支持，预计这项计划项目的应用将对血管重塑有重要的新见解。

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.