Browsing by Subject "exercise training"
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Item Effect of Vascular Heterogeneity, Aging, and Exercise Training on eNOS ? Associated Protein:Protein Interactions(2014-04-14) Luttrell, Meredith JoyEndothelial dysfunction is a major risk factor for the development of cardiovascular diseases, and aging is associated with a gradual decline in endothelial function. Furthermore, endothelial dysfunction in arteries and arterioles supplying skeletal muscle has been implicated in the decline in exercise capacity with aging. Defined as an imbalance between the production and degradation of nitric oxide (NO), limited NO bioavailability is the hallmark characteristic of endothelial dysfunction. Production of NO is controlled by the enzyme endothelial nitric oxide synthase (eNOS), which is regulated in part by post-translational protein modifications. The purpose of this research was to examine the effect of vascular heterogeneity, aging, and endurance exercise training on eNOS-associated protein:protein interactions. Caveolin-1 (Cav1) is a negative regulator of eNOS activity, so that NO production is suppressed when Cav1 is bound to eNOS. Conversely, calmodulin (CaM) and heat-shock protein 90 (Hsp90) are positive regulators of eNOS activity, thus increasing eNOS activity and NO production when either are bound to eNOS. Co-immunoprecipitation was used to determine protein:protein interactions among eNOS and its regulatory proteins throughout the arterial network, from the aorta to third order skeletal muscle arterioles. Results show that eNOS-associated protein:protein interactions vary throughout the arterial network, and Cav1:eNOS and CaM:eNOS interactions are altered with aging. Additionally, endurance exercise training has no effect on the protein:protein interactions examined. In conclusion, eNOS regulation via protein:protein interactions appears to be vessel-specific, and aging has a heterogeneous effect on protein:protein interactions throughout the arterial network.Item Exercise training modulates apoptotic signaling in the aging rat heart(Texas A&M University, 2005-11-01) Kwak, Hyo BumAging is characterized by a progressive decline in cardiac function. A critical contributor to the age-related impairment in heart function is the loss of cardiac myocytes through ??apoptosis??, or programmed cell death. A dramatic increase in the rate of apoptosis has been reported with aging in the rat left ventricle. In contrast, exercise training not only improves cardiac function, but also reduces the risk of heart disease. However, the ability of exercise training to modulate apoptotic signaling and apoptosis in the aging heart remains unknown. Therefore, the purpose of this study was to determine the effects of exercise training on apoptotic signaling and apoptosis in the aging heart. We hypothesized that (1) aging would increase pro-apoptotic signaling and apoptosis in the rat left ventricle, and (2) exercise training would ameliorate upregulation of Bcl-2 family-driven apoptosis in the heart. Four and 25 month old Fischer-344 rats were assigned to four groups: young control (YC), young trained (YT), old control (OC), and old trained (OT). Exercise training groups ran on a treadmill for 60 min/day at 15 m/min (15˚ incline), 5 d/wk for 12 wk. Protein expression of Bax, Bcl-2, caspase-9, and cleaved caspase-3 was measured using Western immunoblot analysis. Apoptosis (DNA fragmentation) was assessed using a cell death detection ELISA. Bax levels in OC were dramatically higher (+176.0%) compared to YC. In contrast, exercise training resulted in a significant decrease (-53.4%) in Bax in OT compared to OC. Bcl-2 levels in OC were lower (-26.3%) compared to YC. Conversely, exercise training significantly increased Bcl-2 levels by 117.8% in OT compared to OC. Caspase-9 levels were higher (+98.7%) in OC than YC, while exercise training significantly reduced caspase-9 levels in YT (-52.6%) and OT (-76.9%), respectively. Aging resulted in a dramatic increase (+122.8%) in cleaved caspase-3 levels and a significant decrease (-32.9%) with exercise training. Finally, apoptosis (DNA fragmentation) significantly increased (+163.8%) with aging and decreased (-43.9%) with exercise training. These novel data indicate that aging increases pro-apoptotic signaling and apoptosis in the left ventricle, while exercise training is effective in diminishing pro-apoptotic signaling and apoptosis in the aging heart.Item Physiological Factors that Modulate Vascular Function: States of Endothelial Dysfunction and Therapeutic Interventions(2013-07-29) Deer, Rachel ReneeThis dissertation investigated the role of two therapeutic interventions (exercise training and hormone replacement therapy) on two different states of endothelial dysfunction, chronic coronary occlusion and aging. Despite remarkable evidence for the therapeutic benefits of physical activity, the mechanisms by which regular exercise improves vascular function in the setting of coronary artery disease are not fully understood. Similarly, the effects of aging and hormone replacement therapy on vascular function are often paradoxical and poorly understood. Thus, the first project utilized a model of chronic coronary artery occlusion to evaluate the effects of exercise training on cellular and molecular adaptations of collateral-dependent coronary vasculature compared to the nonoccluded control. This study provided new evidence that exercise training concomitantly enhanced the contributions of multiple vasodilator mechanisms, including nitric oxide, prostacyclin and BKCa channels to vascular function in the ischemic heart. Increased contribution of multiple vasodilator signaling pathways after exercise training appears to promote compensation or redundancy to ensure adequate vasodilation and coronary vascular blood flow. The second project utilized a model of aging to evaluate the interactive effects of age and hormone replacement therapy on the cellular and molecular mechanisms underlying the regulation of cerebrovascular function. Although the mechanisms underlying the beneficial effects of estrogen on cerebrovascular function have been studied at length, the mechanisms responsible for age-dependent deleterious effects of estrogen are largely unknown. The results of this study revealed that estrogen exerts divergent effects on the cerebrovasculature with advancing age. In younger females, estrogen replacement treatment is beneficial, attenuating vasoconstriction primarily by the COX-1 dependent prostanoid pathway and increased PGI2 production. In contrast, in older reproductively senescent females, estrogen augmented vasoconstriction via the COX-2 dependent prostanoid pathway and increased TXA2 production. A better understanding the mechanisms by which estrogen exerts beneficial versus detrimental effects on the cerebrovasculature may lead to new gender-specific therapeutic agents designed specifically to target the cerebrovascular system and other estrogen-responsive tissues.