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介导和控制跨内皮细胞血浆和血浆之间的水和溶质（小分子和大分子）的交换间质液，简而言之，控制血管通透性，这一功能显然是“至关重要的”。对于所有组织和器官的所有细胞的正常生长、维持和生存也至关重要。炎症中发生的防御机制的重要贡献者。参与跨内皮交换的形态结构已被确定（即小凹、内皮特异性细胞器，例如跨内皮通道、窗孔、囊泡-液泡细胞器以及细胞间连接），除了小窝和细胞间连接连接处，关于结构分子组成的生化证据很少甚至没有本研究提案的主要目标是阐明它们的生物发生和调控。内皮窗孔生物发生的机制除了它们对正常的理解的影响。跨内皮交换的生理过程，该数据可进一步用于研究几种人类疾病的病理生理学，例如肿瘤血管生成、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）、动脉粥样硬化、先兆子痫、中毒性肝损伤和肝硬化，其中这些研究也已被证明可以帮助设计新的策略。所采用的技术是细胞分离、分级分离、生化测定、无细胞测定、转基因动物模型、细胞培养、转染、光学和电子显微镜。