NMR STUDIES OF LIPIDS IN DISEASES

描述：本提案是续期申请的第二次修订。 简而言之，本研究将采用最先进的核磁共振方法， 共振（NMR）光谱来表征的结构 人动脉粥样硬化斑块中的“病理性”脂质（离体）， 分子水平。 魔角旋转（MAS）固态13 C和31 P NMR 将用于识别所有主要斑块脂质并表征其 物理状态（结晶、液晶或液体）， 显微切割和组织破裂。 冠状动脉斑块， 颈动脉和静脉移植物因脂质过多而失败 将研究积累。 假设脂质结构 组织是否与斑块破裂有关将被检测。 nmr数据 导出的也将与磁共振显微图像（MRM）相关， 相同样品以给出分子描述（组成和物理性质 国家）的脂质丰富的地区。 预计这种校准 图像将为患者干预和治疗带来新的策略。 13 C和31 P NMR也将用于研究胆固醇相互作用， 动脉粥样硬化模型系统中的结晶，包括磷脂 双层、细胞膜和细胞如巨噬细胞衍生的泡沫细胞。 这些研究旨在更好地了解过量的 胆固醇在组织中积累，以及如何逆转这一过程。 最后介绍了旋转共振固体核磁共振技术 用于绘制磷脂双层中的分子内距离， 以确定磷脂分子的构象， 双层-水界面，和一个新的二维31 P NMR方法将是 探索区分具有不同头部基团的磷脂， 化学鉴定和定量分析。 通过这些 技术，希望胆固醇结晶对 磷脂界面区域的结构可以用 增强分辨率。

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.