Structure and Function of Endothelial Fenestrae

内皮窗孔的结构和功能

• 批准号: 7929520
• 负责人: RADU VIRGIL STAN
• 金额: $ 46.38万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7929520
• 关键词: 1-Phosphatidylinositol 3-Kinase; Actins; Acute; Allergic; Alzheimer' s Disease; Animal Model; Antibodies; Atherosclerosis; Automobile Driving; Bacterial Infections; Binding; Biochemical; Biogenesis; Biological Assay; Biological Models; Blood; Blood Vessels; Cardiovascular system; Caveolae; Cell Culture Techniques; Cell Separation; Cell membrane; Cells; Chronic; Cirrhosis; Cloning; Cytoskeleton; DNA Sequence Rearrangement; Data; Databases; Defense Mechanisms; Disease; Dominant-Negative Mutation; Drug Delivery Systems; Electron Microscopy; Endocytosis; Endothelial Cells; Endothelium; Event; Excision; Exocytosis; FarGo; Fractionation; Functional disorder; Gene Targeting; Genetic; Genetically Modified Animals; Goals; Graft Rejection; Growth; Growth Factor; Health; Heart; In Situ; Inflammation; Injury; Intercellular Fluid; Intercellular Junctions; Knowledge; Laboratories; Lead; Light; Liquid substance; Literature; Liver; Maintenance; Mediation; Microcirculatory Bed; Molecular; Molecular Structure; Morphology; Mus; Nutrient; Organ; Organelles; Oxygen; Permeability; Pharmaceutical Preparations; Phenotype; Physiological Processes; Plasma; Pre-Eclampsia; Process; Proteins; Reagent; Regulation; Research; Research Proposals; Respiratory Diaphragm; Role; Signal Pathway; Site; Structure; Subcellular structure; System; Techniques; Testing; Tissues; Transfection; Tumor Angiogenesis; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelium; Vascular Permeabilities; Viral; Water; Work; angiogenesis; base; data exchange; design; experience; human disease; mitogen-activated protein kinase p38; molecular marker; novel; novel strategies; solute; transcytosis; tumor; wasting

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，简而言之就是控制血管的通透性。这个功能显然是“至关重要的”， 对于所有组织和器官的所有细胞的正常生长、维持和生存至关重要。这也是 炎症中发生的防御机制的重要贡献者。虽然 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 涉及它们的生物发生和调节。本研究计划的主要目标是阐明 内皮窗孔生物发生机制。除了影响正常的理解之外 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 已证明存在内皮细胞窗孔。这些研究还可以帮助设计新的策略 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。

项目成果

Cells respond to mechanical stress by rapid disassembly of caveolae.

• DOI: 10.1016/j.cell.2010.12.031
• 发表时间: 2011-02-04
• 期刊: Cell
• 影响因子: 64.5
• 作者: Sinha B;Köster D;Ruez R;Gonnord P;Bastiani M;Abankwa D;Stan RV;Butler-Browne G;Vedie B;Johannes L;Morone N;Parton RG;Raposo G;Sens P;Lamaze C;Nassoy P
• 通讯作者: Nassoy P