APOLIPOPROTEIN METABOLISM: REGULATION AND FUNCTION

该计划项目的中心主题是机制和监管 脂蛋白代谢和载脂蛋白在脂质和蛋白质中的作用 脂蛋白动态平衡。胆固醇逆向转运和代谢的研究 将强调间质液脂蛋白代谢。我们的节目 该项目采用多学科方法，涉及生物化学、细胞 生物学、生理学、免疫化学和电子显微镜。我们是 通过利用亚细胞模型来解决这些问题， 在细胞、隔离器官水平和整个动物模型中，包括 人类。我们计划通过从头合成来研究脂蛋白的生物发生。 以及肝脏或肠道细胞器内脂蛋白的重塑。 间质细胞外脂蛋白重塑及其机制的研究 在反向胆固醇运输中可能发挥的作用将继续下去。 最近的研究表明，前βA-I粒子可能在 在胆固醇反向运输中起着关键作用。我们正计划 阐明前β粒子的来源、形成和功能 评价它们在脂蛋白代谢病理生理学中的作用 所有项目中可用的专业知识和技术。 我们对狗的结前外周淋巴的研究将扩展到 人体间质液脂蛋白代谢的研究。我们的方法是 收集人体间质液体不涉及改变 毛细血管渗透性。我们正计划描述人类间质的特征 正常人和不同人群的体液脂蛋白组成 病理条件和评估饮食或药物的影响 干预措施。 我们所有的项目都需要开发微方法，以便 对非常小的样品进行分析。我们正在继续并延长 开发先进的脂蛋白分析方法。 我们相信，这些研究将有助于我们理解 脂蛋白-载脂蛋白代谢及其在脂质中的生理作用 动态平衡。

The central themes of this program project are the mechanism and regulation of lipoprotein metabolism and the role that apoproteins play in lipid and lipoprotein homeostasis. Studies of reverse cholesterol transport and interstitial fluid lipoprotein metabolism will be emphasized. Our program project uses a multidisciplinary approach involving biochemistry, cell biology, physiology, immunochemistry and electron microscopy. We are approaching these problems by utilizing models at the subcellular, cellular, isolated organ level and in whole animal models, including humans. We plan to study biogenesis of lipoproteins by de novo synthesis and remodeling of lipoproteins within hepatic or intestinal organelles. Studies of extracellular lipoprotein remodeling in the interstitium and its possible role in reverse cholesterol transport will be continued. Recent studies have indicated that the pre-beta A-I particles may play a pivotal role in reverse cholesterol transport. We are planning to elucidate the origin, formation and function of the pre-beta particles and evaluate their role in the pathophysiology of lipoprotein metabolism using the expertise and techniques available in all projects. Our studies on prenodal peripheral lymph in dogs will be extended to studies of human interstitial fluid lipoprotein metabolism. Our method for collecting human interstitial fluid does not involve alterations of capillary permeability. We are planning to characterize human interstitial fluid lipoprotein composition in normal individuals and in different pathological conditions and assess the effects of dietary or drug interventions. All of our projects require the development of micromethodologies to allow analysis of very small samples. We are continuing and extending the development of advanced methodologies for lipoprotein analysis. We believe that these studies will contribute to our understanding of lipoprotein-apolipoprotein metabolism and its physiological role in lipid homeostasis.