GENETIC ALTERATIONS ON LIPOPROTEINS AND ATHEROSCLEROSIS

这是一个计划项目补助金的更新，其最初的目标是 是利用转基因动物来了解 脂蛋白代谢和血管生物学方面。我们的目标 保持不变，但我们在脂蛋白生理学的目标是 现在更紧密地关注研究所的优势之一， 也就是说，对生理功能的理解 载脂蛋白E和载脂蛋白B。此外，我们现在有一个主要的 血管生物学和血管基因治疗的新重点。的 研究的重点是代谢和机械后果， 关键分子的表达、修饰或缺失， 脂蛋白代谢，细胞内代谢，血管壁 重塑和动脉粥样硬化。关键的分子， 在脂蛋白转运和代谢中研究的是apo-E和 apo-B在脂蛋白的细胞内生物合成和催化中， 这些分子包括APOBEC-1（负责apo-B的酶 mRNA编辑），微粒体甘油三酯转移蛋白，以及 低密度脂蛋白受体相关蛋白;以及在细胞和 血管壁代谢，它们是NTA 1（APOBEC-I的新靶点） 和转化生长因子（31.当转基因动物， 基因敲除小鼠和体细胞基因改变的动物是主要的模型 系统，许多其他完整的细胞和无细胞模型系统将被 就业。此外，将使用各种各样的技术， 包括来自生物化学、分子生物学、 生物学、遗传学、细胞生物学、动物生理学和显微镜学。 新技术在各项目之间共享，并由 转基因动物核心与代谢及病理 核心，这是大量使用的所有项目。成功 本项目的完成将增进对 脂蛋白代谢的基本机制和血管 壁生物学

This is a renewal of a Program Project Grant whose original goal was to use genetically altered animals to understand significant aspects of lipoprotein metabolism and vascular biology. Our goals remain the same, but our objectives in lipoprotein physiology are now more tightly focused on one of the strengths of the Institute, i.e., the understanding of the physiological functions of apolipoprotein (apo-) E and apo-B. In addition, we now have a major new emphasis in vascular biology and vascular gene therapy. The research focuses on the metabolic and mechanistic consequences of the expression, modification, or deletion of key molecules on lipoprotein metabolism, intracellular metabolism, vascular wall remodeling, and atherosclerosis. The key molecules that will be investigated in lipoprotein transport and metabolism are apo-E and apo-B. In intracellular biosynthesis and catabolism of lipoprotein, these molecules include APOBEC-1 (the enzyme responsible for apo-B mRNA-editing), microsomal triglyceride transfer protein, and the low density lipoprotein receptor-related protein; and in cell and vascular wall metabolism, they are NTA1 (novel target for APOBEC-I) and transforming growth factor (31. While transgenic animals, knockout mice, and somatic gene altered animals are the main model systems, many other intact cell and cell-free model systems will be employed. In addition, a wide variety of techniques will be used, including those from the disciplines of biochemistry, molecular biology, genetics, cell biology, animal physiology, and microscopy. New technologies are shared among the projects and are provided by the Transgenic Animal Core and by the Metabolism and Pathology Core, which are heavily used by all of the projects. The successful completion of this program project will enhance the understanding of fundamental mechanisms of lipoprotein metabolism and vascular wall biology.