Browsing by Subject "high-density lipoprotein"
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Item Identification and Characterization of Caveolins in Mouse Macrophages(2002-12-01) Gargalovic, Peter; Dory, Lad; Basu, Alakananda; McConathy, WalterPeter Gargalovic, Identification and Characterization of Caveolins in Mouse Macrophages. Doctor of Philosophy (Biochemistry and Molecular Biology), December 2002, 206 pp., 3 tables, 41 illustrations, references, 296 titles. The understanding of the mechanisms which control macrophage-lipid management, and their accumulation in atherosclerotic lesions, is of significant importance. Caveolins are proteins associated with cholesterol-rich membrane domains and are intimately linked to the regulation of lipid metabolism and transport. The expression and function of caveolin proteins in three macrophage cell types: thioglycollate-elicited mouse peritoneal macrophages, resident mouse peritoneal macrophages and the J774 macrophage cell line. Data in this work establish that the primary macrophages express caveolin-1 and -2, while J774 cells express only caveolin-2. Immunofluorescence microscopy studies indicate that caveolins in primary macrophages do not colocalize, with caveolin-1 being present on the cell surface and cavelon-2 in the Golgi compartment. Analysis of macrophages also showed that caveolin-1, but not caveolin-2, is present in detergent insoluble lipid raft membranes. While caveolin expression in macrophages is not regulated by sterols, both caveolin isoforms can be secreted from cholesterol-loaded macrophages in the presence of high-density lipoprotein (HDL). Secreted caveolins are part of the complex that has a density similar to HDL, which suggests their association with HDL and potentially a role in HDL-mediated reverse cholesterol transport. The examination of caveolin expression in macrophages shows that caveolin-1, but not caveolin-2 expression is highly upregulated by agents that induce apoptosis in these cells. Induction of caveolin-1 expression precedes DNA fragmentation, is independent of caspase activation, and correlates with the exposure of phosphatidylserine on the cell surface. Importantly, immunofluorescence analysis determined that caveolin-1 in lipid rafts colocalizes extensively with phosphatidylserine present on the surface of apoptotic cells. This study thus identifies caveolin-1 as a specific and early marker of the macrophage apoptotic phenotype. Findings here strongly implicate the involvement of caveolin-1 and lipid rafts in the changes of plasma membrane lipid composition as well as involvement in efficient clearance of apoptotic cells by a phosphatidylserine-mediated mechanism.Item Tracking of Cholesterol Among Individuals With and Without Diagnosed Cardiovascular Disease(2003-05-01) Fisher, Bettina L.; Rene, Antonio; Brant, Larry; Cipher, Daisha J.Fisher, Bettina L., Tracking of Cholesterol Among Individuals With and Without Diagnosed Cardiovascular Disease. Master of Public Health (Epidemiology), May 2003, 46 pp., 6 tables, 5 figures, bibliography, 33 titles. Cardiovascular disease is a major public health problem among the elderly in the United States, and cholesterol is the number one risk factor for coronary heart disease. Tracking is a method of analysis used to identify at-risk subjects at an early age in order to institute preventive measures before physical implications of the disease arise. The purpose of this study is to determine the stability and predictability of total serum cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) values for people with and without diagnosed cardiovascular disease through tracking. Data was obtained from the Baltimore Longitudinal Study on Aging (BLSA) and comprised men, 45 years of age and older who had at least two measurements. The average length of time subjects were in the study was 21 years, and the average number of repeated measurements was seven. The dataset was divided into two subsets – one for subjects entering the study with diagnosed cardiovascular disease, and a second for subjects entering the study without diagnosed cardiovascular disease. Tracking coefficients were measured using the linear regression model and the linear mixed effects model. There was a high degree of tracking for HDL using the linear regression model and the linear mixed effects model (overall dataset: 0.9283, 0.8216 respectively). Comparing tracking coefficients for cholesterol among subjects with and without diagnosed cardiovascular disease (linear mixed effects: 0.6469 and 0.7668; linear regression model: 0.5408 and 0.6022) reveals that the former subset has less stable cholesterol values than that the latter subset. The linear mixed effects model was the best fit for this data, because it corrects for the variation in the BLSA in interperiod and repeated measurements between subjects.