COMPOSITION OF HIGH DENSITY LIPOPROTEIN SUBCLASSES

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，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转运提供了独特的见解，这对在分子水平上理解动脉粥样硬化具有价值。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。到目前为止，我们已经确定了70多个候选蛋白与离散的HDL颗粒，以前没有在人类蛋白质组中识别的几个。质谱鉴定对于鉴定我们没有特异性抗体的蛋白质、低浓度蛋白质和通常认为与HDL无关的蛋白质是最有益的。我们对HDL蛋白组分的理解，包括脂质转移因子，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，载脂蛋白E，载脂蛋白AIV，和载脂蛋白L是至关重要的，我们有能力了解HDL介导的保护冠状动脉疾病的代谢功能。 我们正在使用质谱法研究HDL在9种以前未被识别的HDL代谢单基因疾病中的分子形态，这些疾病是我们通过对极端脂蛋白表型中的突变进行深度测序而确定的。

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.