Cellular and Molecular Mechanisms of Vascular Permeability

血管通透性的细胞和分子机制

• 批准号: 7342057
• 负责人: RADU VIRGIL STAN
• 金额: $ 34.93万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7342057
• 关键词: Acute; Allergic; Alzheimer' s Disease; Animal Model; Antibodies; Atherosclerosis; Automobile Driving; Bacterial Infections; Biochemical; Biogenesis; Biological Assay; Biological Markers; Biological Models; Caveolae; Cell Fractionation; Cells; Chronic; Clathrin-Coated Vesicles; Cloning; Cultured Cells; Data; Databases; Disease; Disputes; Drug Delivery Systems; Electron Microscopy; Endothelial Cells; Endothelium; FarGo; Functional disorder; Gene Targeting; Genetically Modified Animals; Goals; Graft Rejection; Growth; In Situ; Inflammation; Intercellular Fluid; Intercellular Junctions; Knowledge; Laboratories; Lead; Light; Liquid substance; Literature; Mediating; Mediation; Microcirculatory Bed; Microvascular Permeability; Modeling; Molecular; Molecular Structure; Morphology; Organ; Organelles; Pathway interactions; Permeability; Pharmaceutical Preparations; Phenotype; Physiological; Physiological Processes; Physiology; Plasma; Process; Proteins; Range; Rate; Reagent; Regulation; Research; Research Personnel; Research Proposals; Respiratory Diaphragm; Role; Site; Structure; Subcellular structure; System; Techniques; Testing; Tissues; Transfection; Transgenic Mice; Travel; Tumor Angiogenesis; Vascular Endothelium; Vascular Permeabilities; Vesicle; Viral; Water; Work; base; caveolin 1; design; experience; human disease; in vivo; innovation; macromolecule; novel; programs; solute; transcytosis; vascular bed

The main function of the vascular endothelium is the mediation and control of the transendothelialexchanges of water and solutes (both small and large molecules) between blood plasma and theinterstitial fluid, in short the control of vascular permeability. This function is obviously "vital", being critical for normal growth, maintainance and survival of all the cells from all tissues and organs . While the morphological structures involved in transendothelial exchanges have been identified (i.e. caveolae, endothelial specific organelles such as transendothelial channels, fenestrae, vesiculo-vacuolar organelles as well as intercellular junctions), there is very little to no biochemical evidence on the molecular composition of the structures involved, their biogenesis and regulation. The major goals of this research proposal are to elucidate the role of endothelial caveolae and their associated stomatal diaphragms in the transendothelial transport physiology. The findings will also document a novel aspect of the transendothelial transport namely the possibility and ways of its modulation (in rate and components transported). Besides their impact on the understanding of the normal physiological process of the transendothelial transport, the data could be used further in the study of the pathophysiology of several human diseases such as tumor angiogenesis, atherosclerosis, acute and chronic inflammation (both viral and bacterial infections, transplant rejection, allergic encephalomyelytis, Alzheimer disease) where such modulations have been shown to occur. These studies could also provide novel transport related endothelial specific molecular markers that could be used in designing strategies for drugs and gene targeting to selected microvascular beds. The techniques employed are cell fractionation, biochemical assays, cell free-assays, in-vivo transport studies, genetically modified animal models, cell culture, transfections, light and electron microscopy.

血管内皮的主要功能是调节和控制跨内皮的交换 水和溶质（包括小分子和大分子）在血浆和间质液之间，简而言之， 控制血管通透性。这一功能显然是“至关重要的”，对正常生长至关重要， 所有组织和器官的所有细胞的存活。虽然形态结构 参与跨内皮交换的细胞器（即小窝，内皮特异性细胞器 例如跨内皮通道、窗孔、囊泡-空泡细胞器以及细胞间连接）， 关于所涉及的结构的分子组成， 生物发生和调节。这项研究的主要目的是阐明内皮细胞在血管生成中的作用。 小窝及其相关的气孔隔膜在跨内皮运输生理。这些发现 还将记录跨内皮转运的一个新方面，即其可能性和途径， 调制（在速率和传输的组件中）。除了它们对正常人的理解的影响外， 生理过程的跨内皮运输，数据可用于进一步的研究， 几种人类疾病如肿瘤血管生成、动脉粥样硬化、急性和慢性 炎症（病毒和细菌感染、移植排斥、过敏性脑脊髓炎、阿尔茨海默病） 疾病），其中已显示发生这种调节。这些研究还可以提供新的 转运相关的内皮特异性分子标记物，可用于设计药物策略 和基因靶向选定的微血管床。所采用的技术是细胞分级分离， 生物化学测定、无细胞测定、体内转运研究、转基因动物模型、细胞 培养、转染、光学和电子显微镜。