ANIMAL MODELS OF REDOX METABOLISM AND ARTERIAL DYSFUNCTION

概述和具体目标 Core B将通过以下方式为所有四个项目提供支持：1)在本PPG正在研究的转基因和基因敲除小鼠模型中进行血管生理学和药理学实验，以及2)与耶鲁大学小鼠代谢表型中心(YMMC)协调拟议的研究，以获得本计划正在研究的几个小鼠模型的详细体内代谢特征。该核心支持的关于小鼠血管生理学和新陈代谢的拟议研究将为计划拟议的通用实验产生的数据提供关键背景，该实验探索小鼠内皮细胞中的氧化还原生物化学和氧化还原生物标记物。米歇尔博士在本项目期间曾担任动脉功能障碍动物模型核心实验室主任，他是一位经验丰富的血管生物学家，一直参与与pther项目负责人进行富有成效的合作，研究小鼠血管生理学和药理学。新陈代谢研究带头人Gerald Shulman博士(见附信)是YMMC的主任，已经与Plutzky博士和Lee博士合作；Shulman博士将继续在拟议的研究中就实验设计和分析提供咨询，以上所有个别项目描述中都有详细描述。

Overview and Specific Aims Core B will provide support for all four Projects by 1) performing vascular physiology and pharmacology experiments in the transgenic and knockout mouse models being investigated in this PPG, and 2) by coordinating the proposed studies with the Yale Mouse Metabolic Phenotyping Center (YMMC) for the detailed in vivo metabolic characterizations that are planned for several ofthe mouse models being studied in this Program. The proposed studies of mouse vascular physiology and metabolism being supported in this Core will provide a critical context for the data that will be generated by Program's proposed Common Experiment, which explores redox biochemistry and redox biomarkers in mouse endothelial cells. Dr. Michel, who has served as Director of the Animal Models of Arterial Dysfunction Core Lab during the current project period, is an experienced vascular biologist who has been involved in productive collaborations studying murine vascular physiology and pharmacology with the pther Project Leaders. Dr. Gerald Shulman (see attached letter), a leading investigator in metabolism, is the director of the YMMC, and is already collaborating with Drs. Plutzky and Lee; Dr. Shulman will continue to consult on experimental design and analysis in the proposed studies, which are described in detail in all the individual Project descriptions above.