Imaging Lipoprotein-Endothelial Cell Interactions

脂蛋白-内皮细胞相互作用成像

• 批准号: 6951048
• 负责人: JOHN Calvert RUTLEDGE
• 金额: $ 46.65万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-22 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6951048
• 关键词: Raman spectrometry; apolipoprotein E; bioimaging /biomedical imaging; cardiovascular imaging /visualization; cell membrane; clinical research; conformation; dietary lipid; electron spin resonance spectroscopy; human subject; laboratory mouse; membrane lipids; nanotechnology; physical chemical interaction; vascular endothelium; very low density lipoprotein

DESCRIPTION (provided by applicant): The major goal of this proposal is to determine how triglyceride-rich lipoproteins (TGRL) and their associated apoprotein E (apoE) isoforms interact with endothelial cell plasma membrane micro domains, including lipid rafts, in the postprandial state. Our proposal spans the spectrum from detection of single molecules affecting lipoprotein-endothelial cell interactions to individual human feeding studies. Work from our lab and others have led us to propose the following specific aims: Aim 1: To determine the conformational properties of apoE3 and apoE4 present on very-low density lipoproteins (VLDL) in the pre- and postprandial states. Aim 2: To examine apoE3 and apoE4 interactions with endothelial cells in the pre- and postprandial states. Aim 3: To determine how the pre- and postprandial states modify plasma membrane microstructure. We have assembled a unique group with expertise covering structural biology, laser spectroscopy and microscopy, lipid biochemistry, vascular biology and clinical nutrition. The combined expertise of this group will enable us to extend our understanding of how lipoproteins interact with endothelium using advanced imaging techniques at the cellular and molecular level. We expect that the molecular level understanding obtained through the proposed work will mark an important step forward in our basic and clinical understanding of how atherosclerotic cardiovascular disease, the greatest single cause of morbidity and mortality in the U.S., is initiated.

描述（由申请人提供）： 该提案的主要目的是确定富含甘油三酸酯的脂蛋白（TGRL）及其相关的丙蛋白E（APOE）同工型如何与后状态的内皮细胞质膜微型结构型（包括脂质筏）相互作用。我们的建议跨越了影响脂蛋白 - 粘蛋白细胞相互作用到个别人类喂养研究的单分子的检测。我们实验室和其他人的工作使我们提出了以下具体目标： 目的1：确定在前后餐前和餐后状态中极低密度脂蛋白（VLDL）上存在APOE3和APOE4的构象性能。 AIM 2：检查APOE3和APOE4与餐前和餐后状态中内皮细胞的相互作用。 目标3：确定餐前状态和餐后状态如何修改质膜微观结构。 我们组装了一个独特的群体，其专业知识涵盖了结构生物学，激光光谱和显微镜，脂质生物化学，血管生物学和临床营养。该组的组合专业知识将使我们能够使用高级成像技术在细胞和分子水平上使用高级成像技术来扩展对脂蛋白如何与内皮相互作用的理解。我们预计，通过拟议的工作获得的分子水平理解将标志着我们对动脉粥样硬化心血管疾病的基本和临床理解的重要一步，这是美国发病和死亡率最大的最大原因。