Structure and Function of Endothelial Fenestrae

内皮窗孔的结构和功能

基本信息

批准号：
7730256
负责人：
RADU VIRGIL STAN
金额：
$ 46.25万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7730256
关键词：
Actins Acute Adult Allergic Alzheimer&apos s Disease Animal Model Atherosclerosis Automobile Driving Bacterial Infections Biochemical Biogenesis Biological Assay Blood Blood Vessels Breeding CAV1 gene Cardiovascular system Caveolae Cell Culture Techniques Cell Separation Cell membrane Cells Chronic Cirrhosis Cytoskeleton Data Databases Defense Mechanisms Disease Electron Microscopy Electrons Embryo Endocytosis Endocytosis Pathway Endothelial Cells Endothelium Event Excision Exocytosis Fluorescent Probes Fractionation Functional disorder Funding Gene Targeting Genetic Genetically Modified Animals Goals Graft Rejection Growth Heart Image Immunoblotting Immunofluorescence Immunologic In Situ Inflammation Injury Intercellular Fluid Intercellular Junctions Kidney Kidney Glomerulus Knowledge Life Light Liquid substance Literature Liver Maintenance Mediation Microcirculatory Bed Microscopy Molecular Molecular Structure Morphology Mus Nutrient Organ Organelles Oxygen Pancreas Permeability Pharmaceutical Preparations Phenotype Physiological Processes Plasma Play Pre-Eclampsia Process Proteins Regulation Research Research Proposals Respiratory Diaphragm Role Scanning Transmission Electron Microscopy Procedures Small Interfering RNA Staging Structure Subcellular structure System Techniques Testing Tissues Transfection Transgenic Organisms Treatment Efficacy Tumor Angiogenesis Vascular Endothelium Vascular Permeabilities Viral Water Work base data exchange design human disease inhibitor/antagonist novel strategies overexpression solute wasting

项目摘要

The main function of the vascular endothelium is the mediation and control of the transendothelial exchanges of water and solutes (both small and large molecules) between blood plasma and the interstitial fluid, in short the control of vascular permeability. This function is obviously “vital”, being critical for normal growth, maintenance and survival of all the cells from all tissues and organs. It is also an important contributor to the defense mechanisms that occur in inflammation. 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), with the exception of caveolae and the 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 mechanism of endothelial fenestrae biogenesis. Besides their impact on the understanding of the normal physiological process of the transendothelial exchange, the data could be used further in the study of the pathophysiology of several human diseases such as tumor angiogenesis, acute and chronic inflammation (both viral and bacterial infections, transplant rejection, allergic encephalomyelytis, Alzheimer disease), atherosclerosis, preeclampsia, toxic liver injury and cirrhosis where modulations of endothelial fenestrae have been shown to occur. These studies could also help in designing novel strategies for drugs and gene targeting to selected microvascular beds. The techniques employed are cell isolation, fractionation, biochemical assays, cell free-assays, genetically modified animal models, cell culture, transfections, light and electron microscopy.

血管内皮的主要功能是跨内皮的调解和控制血浆与血浆之间的水和太阳能交换（大小分子）间隙流体，简而言之，控制血管通透性。这个功能显然是“至关重要的”，对所有组织和器官的所有细胞的正常生长，维持和存活至关重要。也是炎症中发生的防御机制的重要贡献。而已经鉴定出参与跨内皮交换的形态结构（即小caveolae，，，内皮特异性细胞器，例如跨内皮通道，Fenestrae，Vesiculo-vacuolar 细胞器以及细胞间连接），除了小屋和细胞间外结，关于结构的分子组成几乎没有生化证据涉及的生物发生和调节。这项研究建议的主要目标是阐明内皮芬斯特雷生物发生的机理。除了影响对正常的理解跨内皮交换的生理过程，可以在研究中进一步使用数据几种人类疾病的病理生理，例如肿瘤血管生成，急性和慢性炎症（病毒感染和细菌感染，移植排斥，过敏性脑质体，阿尔茨海默氏病），动脉粥样硬化，前症，有毒肝损伤和肝硬化已显示内皮芬斯特雷发生。这些研究还可以帮助设计新颖的策略药物和基因靶向选定的微血管床。所采用的技术是细胞隔离，分馏，生化测定，细胞自由测定，转基因动物模型，细胞培养，转染，光和电子显微镜。