POLYUNSATURATED FATTY ACIDS AND CELL FUNCTION

项目1涉及多不饱和脂肪酸的影响 多不饱和脂肪酸(PUFA)及其产物对血管内皮细胞和动脉平滑的影响 肌肉细胞功能。目的是确定脂质的作用 由多不饱和脂肪酸衍生的生物介体和氧化产物 血管调节与动脉粥样硬化形成。有五个具体目标。 目标1将描述过氧化物体-β氧化的功能 花生四烯酸，是否存在不同的竞争 N-6和n-3多不饱和脂肪酸进入这一途径。两个人的作用 花生四烯酸通过此途径产生的产物，12：2N-6 和16：3n-6，以及在多大程度上 通路在血管内皮细胞和平滑肌细胞中发挥作用 产生活性氧物种(ROS)。Aim 2将研究 多不饱和脂肪酸氧化产物的代谢 环氧二十碳三烯酸(EETs)、二羟基二十碳三烯酸 (DHETs)和羟基十八碳二烯酸(HoDES) 动脉细胞。微血管和大血管搬运电子内窥镜 将比较血管内皮细胞。假设这些 化合物产生ROS，从而引发低密度脂蛋白氧化 将被测试，并通过转基因来预防这种情况的能力 具有抗氧化酶基因的内皮细胞将被探索。 目标3将研究EETs和其他 含氧花生四烯酸代谢产物诱导内皮细胞 白细胞黏附分子的激活和表达 强调转录和翻译控制。目标4将 利用膜片钳技术验证光滑膜暴露的假设 肌肉中多不饱和脂肪酸、EETs或相关多不饱和脂肪酸的含量升高 氧化产物影响Kplus通道，导致 血管反应性。目标5将检验脂蛋白 脂肪酶诱导富含甘油三酯的脂蛋白和 含有氧化脂质的脂蛋白会对 内皮细胞的功能。这些数据将提供基本的新数据 多不饱和脂肪酸和含氧多不饱和脂肪酸作用机理的研究 产品影响血管功能，而血管功能参与 动脉粥样硬化及其并发症。

Project 1 deals with the effects of polyunsaturated fatty acids (PUFA) and their products on endothelial and arterial smooth muscle cell function. The objective is to determine the role of lipid biomediators and oxidation products derived from PUFA in vascular regulation and atherogenesis. There are five specific aims. Aim 1 will delineate the function of peroxisomal beta-oxidation of arachidonic acid, and whether there is competition between different n-6 and n-3 PUFA for entry into this pathway. The function of two products produced from arachidonic acid by this pathway, 12:2n-6 and 16:3n-6, will be explored, as well as the extent to which this pathway operates in endothelial and smooth muscle cells and generates reactive oxygen species (ROS). Aim 2 will examine the metabolism of PUFA oxidation products such as epoxyeicosatrienoic acids (EETs), dihydroxyeicosatrienoic acids (DHETs), and hydroxyoctadecadienoic acids (HODEs) by the arterial cells. The handling of EETs by microvessel and large vessel endothelial cells will be compared. The hypothesis that these compounds generate ROS and can thereby trigger LDL oxidation will be tested, and the ability to protect against this by transfecting endothelial cells with antioxidant enzyme genes will be explored. Aim 3 will investigate the mechanism by which EETs and other oxygenated arachidonic acid metabolites induce endothelial activation and the expression of leukocyte adhesion molecules, with emphasis on transcriptional and translational control. Aim 4 will utilize patch clamping to test the hypothesis that exposure of smooth muscle to elevated amounts of PUFA, EETs, or related PUFA oxidation products affects Kplus channels, leading to changes in vascular reactivity. Aim 5 will test the hypothesis that lipoprotein lipase induced lipolysis of triglyceride-rich lipoproteins and lipoproteins that contain oxidized lipids can adversely affect the function of endothelial cells. These data will provide basic new insight into the mechanisms by which PUFA and oxygenated PUFA products affect vascular functions that are involved in atherosclerosis and its complications.