School of Public Health
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The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
Note: Prior to July 1, 2007, the School of Public Health was named the College of Health & Human Performance.
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Item EFFECTS OF CARDIOVASCULAR DISEASE AND PHYSICAL INACTIVITY ON THE PARACRINE FUNCTION OF CIRCULATING ANGIOGENIC CELLS(2015) Landers-Ramos, Rian Quinn; Hagberg, James M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Cardiovascular disease (CVD) is the leading cause of death in developed countries. Traditional cardiovascular risk factors account for only a fraction of events related to CVDs, emphasizing the need for investigations into more novel risk factors. Circulating angiogenic cells (CACs) are involved in the repair and maintenance of the vascular endothelium and function mainly through paracrine mechanisms. The studies presented in this dissertation provide new insight into differences in the paracrine actions of CACs as a function of habitual physical activity and CVD. The first study presented identifies, for the first time, that secreted factors from CD34+ and CD34-/CD31+ CACs affect HUVEC tube formation as a function of habitual physical activity. Study #1 identifies inflammatory proteins S100A8 and S100A9 as major factors contributing to the depressed tube formation observed when using CD34-/CD31+ conditioned media (CM) from inactive younger adults compared to endurance-trained athletes. The second study aimed to confirm the effects of S100A8 and S100A9 in CD34-/CD31+ CM on HUVEC tube formation in CVD patient populations compared to endurance-trained athletes. Study #2 found that the CM from non-ST- segment elevation myocardial infarction (NSTEMI) patient CD34-/CD31+ CACs impaired tube formation compared to athletes’ CM, and that pretreatment of HUVECs with an inhibitor for TLR4, a major receptor for S100A8 and S100A9, rescued tube formation to the levels observed when using CD34-/CD31+ CM from athletes. Higher S100A8 and S100A9 content was found in the CM of NSTEMIs compared to athletes. Finally, the study #2 mechanistically demonstrated the direct role of S100A8 and S100A9 on tube formation using recombinant S100A8 and S100A9 and confirmed that these actions were mediated by TLR4. Preliminary data in study #2 suggest that cell surface markers on selected CD34-/CD31+ CACs are inherently different between NSTEMI patients and endurance-trained athletes with lower presence of T-cell and monocyte markers on the CD34-/CD31+ CACs of NSTEMI patients. Collectively, the two studies presented in this dissertation demonstrate that both physical inactivity and CVD alter the paracrine actions of CD34-/CD31+ CACs which in turn impair HUVEC tube formation. These findings are of particular importance as new methods to improve CAC function for therapeutic purposes are being developed.Item The Effect of a 10 day Cessation of Training in Older Endurance Athletes on Pathological Production of Nitric Oxide and Reactive Oxygen Species Levels in Circulating Angiogenic Cells(2015) Corrigan, Kelsey J.; Hagberg, James; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Cardiovascular disease (CVD) is a serious disease, and is the leading cause of death in the United States. Aging and physical inactivity are two well-established risk factors for CVD. Previous research has identified circulating angiogenic cells (CACs) as a novel risk factor for CVD. CAC number and function are affected by aging and exercise. Nitric oxide (NO) and reactive oxygen species (ROS) are intracellular compounds which can affect the health of the vasculature and are also affected by exercise. Endothelial nitric oxide synthase (eNOS) is responsible for NO production within the endothelium, and eNOS "coupling" is a phenomenon that plays a role in the balance between production of ROS and NO. The literature also indicates that NO can be produced in either a pathological or physiological capacity depending on which isoform of NOS produces it. NO and ROS have been previously measured in CACs and have been shown to affect in vivo and in vitro outcomes related to vascular function. Although NO, ROS, and CACs have all been studied in relation to exercise, no previous studies have examined how the cessation of training in older endurance-trained athletes affects these intra-cellular compounds through the eNOS-coupling pathway. The purpose of this study was to examine the effect of a 10-day cessation of exercise training in older endurance-trained athletes on ROS, NO and the eNOS-coupling pathway in CD34+ cells. NO and ROS were measured in isolated fresh CD34+ cells using fluorescent dye assays. The mRNA expression of genes involved in the eNOS-coupling pathway (endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), dihydrofolate reductase (DHFR), and guanosine triphosphate cyclohydrolase 1 (GTPCH1)) were measured using semi-quantitative Polymerase Chain Reaction (Semi-qt PCR). Flow mediated dilation was measured to gain information about endothelial function. No significant differences were detected after the cessation of training in CD34+ intracellular NO or ROS levels. Flow mediated dilation (FMD) also did not change significantly following cessation of training. eNOS mRNA expression was significantly lower following cessation of training but iNOS, DHFR, and GTPCH1 did not change. Taking into consideration the current literature, we expected to see changes in all of the above variables with the cessation of exercise training. There were several limitations present in our study, which could have affected our outcomes. Research in this area, specifically the eNOS coupling pathway, is still very new and this study shows that additional research is still needed to elucidate the underlying mechanisms in CACs.