Theses and Dissertations from UMD
Permanent URI for this communityhttp://hdl.handle.net/1903/2
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
More information is available at Theses and Dissertations at University of Maryland Libraries.
Browse
3 results
Search Results
Item Influence of AT1R polymorphisms and aerobic exercise training on angiotensin II, oxidative stress and urinary nitric oxide(2007-04-26) Fenty, Nicola Melissa; Hagberg, James M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Oxidative stress is implicated in the pathogenesis of cardiovascular disease (CVD) and angiotensin II (AngII), via the type 1 receptor (AT1R), is a major factor contributing to oxidative stress. Protection against oxidative injury is provided by several antioxidants, including superoxide dismutase (SOD). Aerobic exercise training (AEX) is a non-pharmacological intervention that reduces the risk of CVD, partly through reducing levels of oxidative stress. We investigated whether the AT1R A1166C and -825 T/A polymorphisms and AEX influence oxidative stress, urinary NOx and plasma AngII. One hundred sedentary, hypertensive individuals underwent 6 months of standardized AEX. Plasma levels of AngII and SOD, and urinary excretion of NOx and 8-iso-PGF2α were measured before and after AEX. Subject characteristics and baseline values of outcome variables were similar among all genotype groups. Overall, there was a significant increase in 8-iso-PGF2α (p = 0.002) and a significant decrease in NOx excretion (p = 0.0001) however, there were no significant changes in SOD activity or AngII levels with AEX. Neither oxidative stress markers nor urinary NOx were significantly different between genotype groups with AEX. There was a significant difference in AngII levels with AEX between A1166C genotype groups (p = 0.04) resulting in a significant interactive effect of the A1166C polymorphism and AEX on the change in AngII (p < 0.05). The TT genotype group of the -825 T/A polymorphism had a significant reduction (p = 0.02) in plasma AngII, while there was no change in carriers of the A allele. Risk allele analysis revealed that there was a significant reduction in plasma AngII (p = 0.04), a significant increase in 8-iso-PGF2α (p = 0.01) and a significant decrease in urinary NOx (p = 0.0001) with AEX in individuals with 2 risk alleles. Our findings suggest that variation in the AT1R gene is associated with differential changes in plasma AngII but not with oxidative stress. Furthermore, our results may have clinical implications for the prescription of AEX in a population at risk for CVD as exercise intensities that surpass moderate intensity, may attenuate some of the beneficial effects of regular exercise by leading to increased oxidative stress.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 Influence of Vitamin D Receptor Gene Polymorphisms on Changes in Insulin Sensitivity with Aerobic Exercise Training(2005-01-24) Harne, Amanda Janel; Hagberg, James M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The purpose of the study was to examine the influence of the FokI and BsmI polymorphisms of the vitamin D receptor gene on changes in insulin sensitivity with aerobic exercise training in men and women at increased risk for type 2 diabetes mellitus (T2DM). Subjects were genotyped and underwent oral glucose tolerance tests before and after six months of training. Due to mis-genotyping of the BsmI polymorphism, results for that variant were not reported. There were no significant differences between FokI genotype groups in insulin sensitivity before or after training. However, among subjects who completed training, FF homozygotes had significantly higher baseline fasting glucose and insulin levels than f allele carriers. While the FokI polymorphism does not appear to mediate training-induced changes in indices of glucose and insulin metabolism, it may influence fasting glucose and insulin levels and the development of insulin resistance in individuals at increased risk for T2DM.