APOLIPOPROTEIN METABOLISM: REGULATION AND FUNCTION

该项目的中心主题是机制和监管 以及载脂蛋白在脂质代谢中的作用， 脂蛋白稳态 胆固醇逆向转运的研究 强调组织液脂蛋白代谢。 我们的节目 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 通过利用亚细胞模型来解决这些问题， 细胞、离体器官水平和整个动物模型，包括 人类 我们计划通过从头合成来研究脂蛋白的生物合成 以及肝或肠细胞器内脂蛋白的重塑。 黄芪细胞外脂蛋白重构及其机制的研究 在胆固醇逆向转运中的可能作用将继续。 最近的研究表明，前β A-I颗粒可能在细胞内起着重要的作用。 在胆固醇逆向转运中起关键作用。 我们计划 阐明前β粒子的起源、形成和功能， 评价其在脂蛋白代谢的病理生理学中的作用， 所有项目中可用的专业知识和技术。 我们对狗结前外周淋巴的研究将扩展到 人间质液脂蛋白代谢的研究。 我们的方法 收集人类组织液不涉及改变 毛细血管通透性 我们正计划对人类组织间质 在正常人和不同的人中， 病理状况，并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观方法学， 分析非常小的样本。 我们将继续并扩大 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了解 脂蛋白-载脂蛋白代谢及其在脂质中的生理作用 体内平衡

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.