COMPOSITION OF HIGH DENSITY LIPOPROTEIN SUBCLASSES

高密度脂蛋白亚类的组成

• 批准号: 8169731
• 负责人: JOHN P KANE
• 金额: $ 1.06万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-12 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169731
• 关键词: Antiatherogenic; Antibodies; Apolipoprotein E; Atherosclerosis; Cholesterol; Computer Retrieval of Information on Scientific Projects Database; Coronary Arteriosclerosis; Disease; Funding; Grant; High Density Lipoproteins; Human; Institution; Laboratories; Lipids; Lipoproteins; Mass Spectrum Analysis; Mediating; Metabolic; Metabolism; Methods; Molecular; Mutation; Phenotype; Plasma; Play; Protease Inhibitor; Proteins; Proteome; Research; Research Personnel; Resources; Role; Source; Transfer Factor; Transferase; United States National Institutes of Health; hepatic lipase; insight; lipid metabolism; metabolic abnormality assessment; particle; phosphatidylcholine transfer protein

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our studies of metabolism, of high density lipoproteins (HDL) offer unique insights into lipid metabolism and transport that will be of value in understanding atherosclerosis at a molecular level. Methods developed in our laboratory have allowed us to document previously unreported molecular subspecies of HDL, each of which may play a specific antiatherogenic role associated with HDL. HDL subspecies purified from plasmas of normo- and dyslipidemic subjects reveal a variety of proteins. To date we have identified over seventy candidate proteins that associate with discrete HDL particles, several not previously recognized in the human proteome. Mass spectroscopic identification is of most benefit for the identification of proteins for which we have no specific antibodies, for proteins of low concentration, and for proteins which are not generally considered to associate with HDL. Our understanding of the HDL protein components consisting of lipid transfer factors such as cholesterol transfer protein, lecithin:cholesterol transferase, phosholipid transfer protein, hepatic lipase, plasma protease inhibitors, apoE, apoAIV, and apoL is paramount to our ability to understand the metabolic function of HDL-mediated protection in coronary artery disease. We are using mass spectrometry to study the molecular speciation of HDL in nine previously unrecognized monogenic disorders of HDL metabolism which we have identified by deep sequencing of mutations in extreme lipoprotein phenotypes.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们对高密度脂蛋白 (HDL) 代谢的研究为脂质代谢和运输提供了独特的见解，这对于在分子水平上了解动脉粥样硬化具有重要价值。我们实验室开发的方法使我们能够记录以前未报道的 HDL 分子亚种，每种分子亚种都可能发挥与 HDL 相关的特定抗动脉粥样硬化作用。 从血脂正常和血脂异常受试者的血浆中纯化的 HDL 亚种揭示了多种蛋白质。迄今为止，我们已经鉴定了超过 70 种与离散 HDL 颗粒相关的候选蛋白，其中有几种以前在人类蛋白质组中未被识别。质谱鉴定最有利于鉴定我们没有特异性抗体的蛋白质、低浓度的蛋白质以及通常被认为与 HDL 不相关的蛋白质。我们对由脂质转移因子（如胆固醇转移蛋白、卵磷脂：胆固醇转移酶、磷脂转移蛋白、肝脂肪酶、血浆蛋白酶抑制剂、apoE、apoAIV 和 apoL）组成的 HDL 蛋白成分的了解，对于我们了解 HDL 介导的冠状动脉疾病保护的代谢功能至关重要。 我们正在使用质谱法研究九种以前未被识别的 HDL 代谢单基因疾病中 HDL 的分子形态，我们通过对极端脂蛋白表型的突变进行深度测序来识别这些疾病。