Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item Effect of long-term exercise on endothelial progenitor cells in healthy humans(2008-04-24) Witkowski, Sarah; Hagberg, James M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Endothelial progenitor cells (EPCs) are derived from the bone marrow and have been found to play a role in postnatal neovascularization and re-endothelialization. Reduced EPC number and function have been associated with death from cardiovascular diseases, CVD risk factors, and endothelial dysfunction. Oxidative stress, specifically, oxidized LDL (OxLDL) has been shown to decrease EPC number and function, and increase EPC senescence in vitro. Regular physical activity is related to lower rates of CVD; however the mechanisms underlying the benefits of exercise in the prevention of CVD are not fully clear. Exercise may improve the number, and function of EPCs while improving oxidative stress status. The primary purpose of this study was to compare CD34+/KDR+ EPC number, EPC clonogenic capacity, and senescence, in healthy men that have participated in greater than 20 years of moderate- to high-intensity exercise with low-active control subjects. To assess the effect of physical inactivity on these markers, a subset of exercisers (n=10) stopped exercising for 10 days after which, measures of EPC number, colony forming units, and senescence, endothelial function and oxidative stress were re-evaluated. Results showed that, CD34+/KDR+ cell number, CFU-Hill colonies, and EPC senescence were not statistically different between athlete and control groups. CD34+/KDR+ cell number was closely related to endothelial function. Specifically, the forearm blood flow response to reactive hyperemia was correlated with CD34+/KDR+ number in sedentary participants. Additionally, 5 athletes significantly decreased their CD34+/KDR+ number, which was related to a significant decline in endothelial function, indicating that regular physical activity is important for some athletes to maintain healthy endothelial function, perhaps through the maintenance of elevated number of circulating CD34+/KDR+ cells. CFU-Hill colony number was strongly correlated with hyperemic blood flow response in control participants and related to oxLDL independent of physical activity status. Athletes who participated in 10-days of exercise detraining demonstrated a significant decrease in EPC senescence, which was related to improved total antioxidant capacity. Overall, these results show that CD34+/KDR+ number is closely related to endothelial function. Moreover, the function of EPCs appears to be affected by oxidative stress and antioxidant availability.Item LOX-1 genotype, dietary fat intake, and aerobic exercise training: Influence on endothelial function, oxidative stress, lipoprotein-lipids, and soluble LOX-1(2006-07-25) Ellis, Tina Janelle; Hagberg, James M.; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The lectin-like oxidized LDL receptor (LOX-1) is the major receptor for oxidized LDL (ox-LDL) in endothelial cells and plays a major role in the initiation and progression of atherosclerosis. Ox-LDL via LOX-1 causes endothelial activation and injury, induces lipid peroxidation, and alters inflammatory gene expression, and variation in the LOX-1 gene has been associated with cardiovascular disease risk. In addition, a soluble form of LOX-1 has been identified in plasma and may predict atherosclerotic disease progression. Thus, the purpose of this study was to investigate the effect of the LOX-1 3'UTR C/T and G501C polymorphisms on endothelial function, oxidative stress, plasma lipoprotein-lipids, and soluble LOX-1. The effect of these polymorphisms on the responses to dietary fat intake and aerobic exercise training was also examined. Forearm blood flow was measured using venous occlusion plethysmography at rest and during reactive hyperemia, and plasma levels of nitrates/nitrites, nitrotyrosine, ox-LDL, total antioxidant capacity, lipoprotein-lipids, and soluble LOX-1 were measured before and after six months of aerobic exercise training. The dietary ratio of polyunsaturated fat to saturated fat (P:S ratio) was determined using 7-day food records. The 3'UTR/CC and 501GC+CC groups had significantly higher baseline soluble LOX-1 levels than the CT/TT and GG groups, respectively. The G501C polymorphism was a significant predictor of baseline soluble LOX-1 levels, even after accounting for age, gender, race, BMI, and the 3'UTR polymorphism (p=0.024). There was a significant interaction between the 3'UTR polymorphism and dietary fat intake for plasma ox-LDL levels (p=0.011). At a high P:S ratio, the 3'UTR/CC group had significantly higher ox-LDL levels than the TT group (p=0.025). The opposite relationship was found at a low P:S ratio (p=0.044). The 3'UTR polymorphism also influenced changes in plasma TG levels with exercise training (p=0.036), while the G501C polymorphism influenced changes in soluble LOX-1 levels (p=0.012). In conclusion, variation in the LOX-1 gene does not appear to be associated with endothelial function, oxidative stress, or plasma lipid levels, but may influence changes in these variables in response to dietary fat intake and exercise training. Moreover, polymorphisms in LOX-1, especially the G501C polymorphism, may regulate circulating levels of soluble LOX-1.Item NFKB1 Gene Promoter Polymorphism and Unidirectional Laminar Shear Stress: Implications for NF-kB Activation, eNOS Protein Expression and Endothelial Function(2006-06-04) Park, Joon Young; Brown, Michael D.; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Exercise stimulus can be defined as endothelial wall shear stress. In the endothelial cells, the nuclear factor-kappa B (NF-κB) is an important intracellular signaling molecule by which changes in wall shear stress, sensed by mechanosensors, are transduced into the nucleus to initiate downstream eNOS gene expression. Recently, a polymorphism in the promoter region of the gene encoding a p50/p105 NF-κB subunit, NFKB1, has been identified. The NFKB1 ATTG insertion (I) / deletion (D) (NFKB1 I/D) promoter polymorphism transcriptionally regulates NFKB1 gene expression. However, the functional significance of this polymorphism has not been elucidated in endothelial cells under LSS and in endothelial function in humans. Therefore, the purpose of this study was to investigate whether the NFKB1 I/D promoter polymorphism had functional genetic properties in human umbilical vein endothelial cells (HUVECs) under physiological levels of unidirectional laminar shear stress (LSS), and further, whether the polymorphism was associated with changes in endothelial function after endurance exercise training in pre- and stage I hypertensive individuals. The major findings of the present study were that 1) a protein present in HUVECs preferentially and specifically binds to the I allele promoter compare to the D allele; 2) the I allele had significantly higher promoter activity than the D allele; and accordingly, the II homozygote cells had higher p50/p105 NFKB1 protein levels than the DD homozygote cells; 3) the II homozygote cells showed a greater increase in eNOS protein levels than the DD homozygote cells under unidirectional LSS; and 4) the I-allele carrier group had a greater reactive hyperemic forearm blood flow response, a measure of endothelial function, before exercise training; however, the NFKB1 I/D polymorphism was not significantly associated with the differential changes in endothelial function following exercise training. These results have potential clinical implications for endothelial dysfunction that are related to the development and progression of atherosclerosis and cardiovascular disease. In addition, our findings provide insight into the molecular mechanisms involved in the intracellular signaling transduction process of eNOS gene expression and function of the NFKB1 gene promoter region.