ENDOTHELIUM AND VASCULAR FUNCTION

本计划项目申请是通过之前广泛的 所有参与研究的调查人员的合作努力 血管内皮细胞在血管调节中的可能作用 在多种组织中的生理和病理生理功能 各州。研究人员代表了几个相关的研究学科： 生物化学、细胞生物学、生理学和药理学。共同的主题 在这些项目中，有一项是对和的特定生物学作用的兴趣 来自内皮细胞的局部释放的介质之间的相互作用。 二十烷基类化合物、氧自由基和其他内皮依赖性物质 血管活性因子。许多参与调查的人已经在 这一领域的前沿研究及其合作将提供 对每个人的研究工作都是一种推动。我们预计，结果是 在我们的协调计划中，血管内皮细胞介质在血液中的作用 血管生物学及其在疾病状态中的可能作用将成为 更清楚了。项目1将评估a)激活 血小板和白细胞中的环氧合酶/磷脂酶A2途径和b) 细胞间转移、同化及其代谢物的作用 血管内皮细胞和血管功能的途径。项目2将 阐述了活性氧代谢物调节的作用方式 血管紧张素在体外大冠状动脉内皮细胞中的作用 细胞在释放这些物种。项目3将调查 肺组织中二十烷类化合物和氧自由基类物质的释放 内皮细胞及其在急性肺损伤中的作用。项目4将 内源性血管活性物质在体内的作用及相互作用研究 内皮源性松弛因子(EDRF)在血管紧张素转换酶抑制剂中的作用 微血管功能。项目5的目标是检查 血管内皮细胞因子(前列腺素，EDRF)在体内的作用 冠状动脉内径的调节及其在冠状动脉病变中的作用 冠状动脉血流量的控制。两个核心设施将支持 研究项目：行政核心和细胞培养核心。

This Program Project application was made possible by previous extensive collaborative efforts of investigators who are all involved, in studying the possible role of endothelial cell sin the regulation of vascular function in a variety of tissues in physiological and pathophysiological states. The investigators represent several related research disciplines: Biochemistry, Cell Biology, Physiology and Pharmacology. The common theme among the projects is an interest in the specific biological role of and interaction among locally released mediators from endothelial cells- e.g. eicosanoids, oxygen free radical species and other endothelium dependent vasoactive factors. Many of the participating investigators have been in the forefront of research in this area and their collaboration will provide an impetus to everyone's research effort. We anticipate, that as a result of our coordinated program, the role of endothelial mediators in blood vessel biology as well as their possible role in disease states will become clearer. Project 1 will evaluate a) activation of the epoxygenase/phospholipase A2 pathway in platelets and leukocytes and b) transfer between cells, assimilation, and effect of metabolites of this pathway on endothelial cells and blood vessel function. Project 2 will address the mode of action of reactive oxygen metabolites on regulation of tone in large coronary arteries in vitro as well as the role of endothelial cells in the release of these species. Project 3 will investigate the release of eicosanoids and oxygen radical species from pulmonary endothelial cells and their role in acute lung injury. Project 4 will study in vivo the role and interaction with other endogenous vasoactive agents of endothelium-derived relaxing factor (EDRF) in the control of microvascular function. Project 5 will have as its goal to examine the role, in vivo, of endothelial factors (prostaglandins, EDRF) in the regulation of coronary artery diameter and their contribution to the control of coronary blood flow. Two core facilities will support the research projects: an Administrative core and a Cell Culture Core.