PATHOPHYSIOLOGY O THE ENDOTHELIUM

血管的各种成分之间的相互作用 壁-内皮、平滑肌、结缔组织-以及可溶性和 血液中的细胞成分，显著参与了 炎症、血栓形成、动脉粥样硬化的病理生理学 免疫性血管损伤。本计划项目的总体目标 是研究某些相互作用的机制，在这些相互作用中 血管内皮细胞起着核心作用。项目1将研究 白细胞与内皮细胞的黏附使用细胞生物学， 体外免疫学和生化方法；项目2将研究 培养的血管内皮细胞和平滑肌细胞的大分子内吞作用 一种与物质从血液转移到 间质以及细胞内代谢；项目3将研究 单核/巨噬细胞产生间充质细胞生长因子(S)及 这些细胞在体内内膜(平滑肌)增生中的作用； 项目4将使用动物模型来检查非剥离的作用 血管内皮损伤与血清脂蛋白和血小板的相互作用 在动脉粥样硬化的发病机制中；项目5将研究 血管性血友病患者血小板膜糖蛋白1b的生化相互作用 蛋白质和内皮下基质；项目6将检查细胞和 血管内皮细胞介导的Smooth反应的生化机制 肌肉细胞到血管活性激素；项目7将研究各种 内皮细胞和淋巴细胞在体外的免疫相互作用。A单元格 培养核心将提供具有良好特色的血管和 非血管细胞类型，以及体外模型系统的经验 研究细胞间的相互作用。形态学核心将提供专业知识 以及扫描和透射电子显微镜的设施， 超微结构免疫细胞化学、放射自显影等技术。 生化核心将为气体和高压提供设施 液体色谱学。这些研究因此结合了细胞生物学， 生化、免疫学和实验病理学方法 探讨血管疾病的发病机制。

Interactions among the various components of the vascular wall---endothelium, smooth muscle, connective tissue---and the soluble and cellular constituents of the blood, are prominently involved in the pathophysiology of inflammation, thrombosis, atherosclerosis and immunologic vascular injury. The overall objective of this Program Project is to examine the mechanisms of certain of these interactions in which the endothelium plays a central role. Project 1 will study the mechanisms of leukocyte adhesion to endothelial cells using cell biological, immunological and biochemical approaches in vitro; Project 2 will study macromolecular endocytosis in cultured endothelial and smooth muscle cells, a process relevant to the transfer of substances from blood to interstitium, as well as intracellular metabolism; Project 3 will study the production of mesenchymal cell growth factor(s) by monocyte/macrophages and the role of these cells in intimal (smooth muscle) hyperplasia in vivo; Project 4 will use animal models to examine the role of non-denuding endothelial injury and the interaction of serum lipoproteins and platelets in the pathogenesis of atherosclerosis; Project 5 will examine the biochemical interactions of platelet glycoprotein 1b, von Willebrand's protein and the subendothelial matrix; Project 6 will examine cellular and biochemical mechanisms included in endothelial-mediated responses of smooth muscle cells to vaso-active hormones; Project 7 will study various immunological interactions of endothelium and lymphocytes in vitro. A Cell Culture Core will provide well characterized cultures of vascular and non-vascular cell types, and experience with in vitro model systems for studying cellular interactions. A Morphology Core will provide expertise and facilities for scanning and transmission electron microscopy, ultrastructural immunocytochemistry, autoradiography and other techniques. A Biochemistry Core will provide facilities for gas and high pressure liquid chromatography. These studies thus combine cell biological, biochemical, immunological and experimental pathological approaches to probe vascular disease mechanisms.