Chemical Synthesis and Lipid Peroxidation Analytical Core

该项目的总体目标是评估高密度脂蛋白功能障碍对三种增加动脉粥样硬化风险的情况的贡献：家族性高胆固醇血症、慢性肾病和类风湿性关节炎。这些条件下高密度脂蛋白功能障碍的一个机制似乎是氧化应激的存在，这导致了本项目中的一个主要假设：在这些条件下高密度脂蛋白的过氧化导致它变得功能障碍。Core C将通过测量HDL中各种脂质过氧化产物的水平，并通过提供试剂直接测试这些氧化产物对HDL功能障碍的贡献，来协助这项工作。Core C有三个目标：1)合成将在所有3个项目中使用的两类化合物。第一个将是合成异前列腺素产品，包括f2 -异前列腺素含有磷脂、γ -酮醛（异戊二醇/异戊二醇）和非活性类似物，这些产品将主要用于项目3。第二类化合物将是醛清除剂及其无活性类似物，这将在所有3个项目中使用。2)使用质谱技术定量临床和动物样品中的脂质过氧化产物。这些产品将包括f2 -异前列腺素、异葡聚糖-赖氨酸加合物、异葡聚糖- pe加合物和mda -赖氨酸交联。3)定量小鼠血浆中醛类清除剂及其无活性类似物的水平，这些化合物包括水杨胺、4-水杨胺、戊基吡哆胺和戊基吡哆醇。这一服务将被所有3个项目使用。

The overall aim of the program project is to assess the contribution of HDL dysfunction to three conditions that increase risk for atherosclerosis: familial hypercholesterolemia, chronic kidney disease, and rheumatoid arthritis. One mechanism of HDL dysfunction that these conditions appear to share is the presence of oxidative stress, which has led to one of the main hypotheses in this program: that peroxidation of HDL in these conditions causes it to become dysfuncfional. Core C will assist in this endeavor by measuring levels of various products of lipid peroxidation in HDL and by providing reagents to directly test the contribution of these oxidized products to HDL dysfunction. Core C has three aims: 1) To synthesize two classes of compounds that will be utilized in all 3 Projects. The first will be synthetic isoprostane products including F2-isoprostane containing phospholipids, gamma-ketoaldehydes (isolevuglandin/isoketal), and inactive analogs which will be used primarily by project 3. The second class of compounds will be aldehyde scavengers and their inactive analogs which will be used by all 3 projects. 2) To quantify lipid peroxidation products in clinical and animal samples using mass spectrometric techniques. These products will include F2-isoprostane, isolevuglandin-lysine-adducts, isolevuglandin-PE adducts, and MDA-lysine crosslinks. This service will be utilized by all 3 Projects. 3) To quantify plasma levels of aldehydes scavengers and their inactive analogs in mice administered these compounds which include salicylamine, 4-salicylamine, pentylpyridoxamine, and pentylpyridoxine. This service will be utilized by all 3 projects.