Molecular & functional aspects of vascular permeability

血管内皮的主要功能是介导和控制血浆和间质液之间的水和溶质（小分子和大分子）的跨内皮交换。 根据所有组织和器官的所有细胞对它的依赖性来判断，这种功能显然是“至关重要的”。 虽然已经确定了跨内皮交换中涉及的形态结构（即小窝、跨内皮通道、窗孔和细胞间连接），但有关所涉及结构的分子组成、其生物起源和调节的生化证据很少或没有。 本研究的主要目的是阐明气孔膜和气孔窗等内皮细胞分化的化学组成和功能。 该发现还将记录跨内皮转运的一个新方面，即其调节的可能性和方式（在速率和转运组分中）。 除了它们对理解跨内皮运输的正常生理过程的影响之外，这些数据还可以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、糖尿病、视网膜病、银屑病、肺、纤维化、血小板减少症、过敏性脑脊髓炎、动脉高血压），其中已经显示发生这种运输调节。 这些研究还可以提供新的运输相关的内皮特异性分子标记物，可用于设计药物和基因靶向选定的微血管床的策略。 所采用的技术是细胞分级分离、无细胞测定、体内筛选方法、二维电泳、细胞培养、转染、光学和电子显微镜。

The main function of vascular endothelium is the mediation and control of transendothelial exchanges of water and solutes (both small and large molecules) between blood plasma and the interstitial fluid. This function IS OBVIOUSLY "vital", judged on the dependency on it of all the cells from all tissues and organs. While the morphological structures involved in transendothelial exchanges have been identified (i.e. caveolae, transendothelial channels, fenestrae and 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 specific chemical composition and function of the endothelial differentiations such as fenestrae and caveolae and their stomatal diaphragms. The finding 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 (e.g. tumor angiogenesis, diabetes, retinopathy, psoriasis, pulmonary, fibrosis, thrombocytopenia, allergic encephalomyelitis, arterial hypertension) where such transport 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, cell free-assays, in-vivo screening methods, two- dimensional electrophoresis, cell culture, transfections, light and electron microscopy.