NMR STUDIES OF LIPIDS IN DISEASES

描述：本提案是续签申请的第二次修订。 简而言之，这项研究将应用最先进的核磁方法 用核磁共振波谱表征化合物的结构 人动脉粥样硬化斑块(体外)中的“病理性”脂质 分子水平。魔角旋转(MAS)固态13C和31P核磁共振 将用于识别所有主要的斑块脂质并表征其 物理状态(晶态、液晶态或液态) 组织的显微解剖和剥离。冠状动脉上的斑块， 因脂质而失败的颈动脉和静脉移植物 将对积累进行研究。关于脂质结构的假设 组织是否与斑块破裂有关将接受检测。核磁共振数据 衍生的还将与磁共振显微图像(MRM)相关联 相同的样品来给出分子描述(组成和物理 国家)的类脂富集区。预计此次校准 图像将为患者干预和治疗带来新的策略。 ~(13)C和~(31)P核磁共振也将用于研究胆固醇相互作用和 动脉粥样硬化模型体系中的结晶，包括磷脂 双层、细胞膜和巨噬细胞来源的泡沫细胞等。 这些研究的目的是为了更好地理解过度 胆固醇在组织中积累，以及这一过程如何逆转。 最后，旋转共振固体核磁共振技术将是 用于按顺序绘制磷脂双层分子内距离图 为了确定磷脂分子的构象 一种新的二维31P核磁共振方法将是 用于区分不同头基磷脂的探索 化学鉴定和定量分析。通过这些 技术，希望胆固醇结晶的影响在 磷脂界面区的结构可以用 增强的分辨率。

DESCRIPTION: This proposal is a second revision of a renewal application. Briefly, this study will apply state-of-the-art methods of nuclear magnetic resonance (NMR) spectroscopy to characterize the structures of "pathological" lipids in human atherosclerotic plaques (ex vivo) at a molecular level. Magic angle spinning (MAS) solid-state 13C and 31P NMR will be used to identify all major plaque lipids and characterize their physical state (crystalline, liquid crystalline, or liquid) without microdissection and disruption of tissue. Plaques from coronary arteries, carotid arteries, and vein grafts that have failed as a result os lipid accumulation will be studied. The hypothesis that lipid structural organization is related to plaque rupture will be tested. The NMR data derived will also be correlated with magnetic resonance microimages (MRM) of the same sample to give a molecular description (composition and physical states) of lipid-rich regions. It is expected that this calibration of images will lead to new strategies for patient intervention and treatment. 13C and 31P NMR will also be used to study cholesterol interactions and crystallization in model systems for atherosclerosis, including phospholipid bilayers, cell membranes and cells such as macrophage-derived foam cells. These studies are designed to gain a better understanding of how excess cholesterol accumulates in tissues and how this process can be reversed. Finally, the technique of Rotational Resonance Solid-State NMR will be employed to map intramolecular distances in phospholipid bilayers in order to determine the conformation of phospholipid molecules at the bilayer-aqueous interface, and a new two-dimensional 31P NMR method will be explored to discriminate phospholipids with different headgroups for chemical identification and quantitative analysis. Through these techniques, it is hoped that the effects of cholesterol crystallization on the structure of the phospholipid interfacial region can be studied with enhanced resolution.