This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Our studies of lipoprotein metabolism, in particular, the 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 fifty-three candidate proteins that associate with discrete HDL particles. Among these , we have also discovered a new protein, designated apoL-1, that is associated with two discrete HDL species. While protein compositions of some HDL subspecies have been identified by Western blotting, we seek to obtain unequivocal characterization by mass spectroscopy especially in cases were our antibodies produce questionable identities. This frequently results from poor antibody specificity and recognition. 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 have now begun to study the role of lipid transport in the retinal pigment epithelial cells, because they are key elements in human macular degeneration, the major cause of blindness in individuals over fifty years of age. This involves the identification of proteins expressed by the retinal cells, using mass spectrometry.
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