COMPOSITION OF HIGH DENSITY LIPOPROTEIN SUBCLASSES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们对高密度脂蛋白(高密度脂蛋白)代谢的研究提供了对脂代谢和运输的独特见解，这将有助于在分子水平上理解动脉粥样硬化。我们实验室开发的方法使我们能够记录以前未报道的高密度脂蛋白分子亚类，每个亚类都可能发挥与高密度脂蛋白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提纯的高密度脂蛋白亚型揭示了多种蛋白质。到目前为止，我们已经确定了70多个与离散的高密度脂蛋白颗粒相关的候选蛋白质，其中一些以前在人类蛋白质组中没有被识别。对于我们没有特异性抗体的蛋白质、低浓度蛋白质以及通常认为与高密度脂蛋白无关的蛋白质的鉴定，质谱学鉴定是最有利的。我们对包括胆固醇转移蛋白、卵磷脂：胆固醇转移酶、磷脂转移蛋白、肝脂酶、血浆蛋白水解酶抑制物、apoE、apoAIV和APOL等脂转移因子的高密度脂蛋白组成的了解，对于我们理解高密度脂蛋白介导的冠状动脉疾病保护的代谢功能至关重要。 我们正在使用质谱仪来研究之前未发现的9种高密度脂蛋白代谢单基因疾病的高密度脂蛋白分子形态，这些疾病是通过对极端脂蛋白表型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.