The Quantitative and Functional HDL Core (Core B) will provide the powerful tools of modern mass spectrometry and complex data set analysis to Program Project Grant (PPG) investigators. The Core will also provide lipoprotein isolation, measurement of lipoprotein particle concentration using calibrated Differential Mobility Analyzer, and HDL functional assays. The Core will permit structural identification and quantitation of myeloid-cell, HDL, and adipocyte-related biomolecules, evaluation of HDL function and measurement of HDL particle number (HDL-P). Core personnel are proficient in 1- and 2-dimensional liquid chromatography-electrospray ionization-MS/MS analysis (shotgun proteomics) of complex biological mixtures of proteins, with a particular emphasis on the lipoprotein proteomes. In the previous funding cycle this Core established precise methods for quantitation of HDL proteome, measurement of cholesterol efflux capacity, and measurement of the plasma HDL-P concentration. We anticipate that all investigators will take advantage of these capabilities in the next funding period. In addition to providing instrumental capabilities and bioinformatics tools, Core B staff will provide consultation and collaboration on the application of mass spectrometry to the Program Project, and integration and analysis of complex datasets. This will include development of new analytical methods targeted at achieving the research objectives of the Program's investigators. Core B will optimize the efficiency and cost-effectiveness through which these services are provided to PPG investigators by providing a central laboratory. This avoids the need for individual PPG investigators to maintain the required instrumentation in their own laboratories and avoids the high cost of commercial mass spectrometric services. By centralizing and standardizing procedures, Core B will provide a common set of analytical tools that will lead to a unified understanding of molecular mechanisms involved in the physiologic and pathophysiologic processes of diabetic vascular disease.
Diabetes and the metabolic syndrome are two major risk factors for the development of cardiovascular disease. The goal of Core B is to provide services that help Program Project investigators identify the pathways associated with these disorders that impair the cardioprotective effects of HDL.
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