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The impact and mechanism of interaction on exercise-derived microvesicles on cultured endothelial cells
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Author (aut): Wilson, Melissa Maree
Thesis advisor (ths): Rakobowchuk, Mark E.
Degree committee member (dgc): MacKay, Mairi
Thesis advisor (ths): Ross Friedman, Cynthia M.
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Degree granting institution (dgg): Thompson Rivers University. Department of Biological Sciences
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Abstract
Microvesicles (MV) were once thought to be inert cellular fragments; however, a large body of research suggests they are bioactive components involved in intercellular communication and altering physiological processes. As these 100 nm – 1 µm plasma membrane-derived vesicles are formed from many cell types, they vary significantly in composition and function. Recently, it has been shown that high intensity exercise increases the concentration of circulating platelet-derived MVs. While the physiological role of these MVs is unknown, they have been shown to improve the functionality of endothelial cells, indicating a potential for mediating the adaptive effects of exercise on the cardiovascular system. The present study aims to further examine the effects of these exercise-derived MVs on the endothelium, as well as investigate the mechanism by which MVs and endothelial cells interact. Exercise trials were performed to produce blood MV samples from eleven participants. To test the effects of exercise-derived MVs, cultured endothelial cells were treated with MV samples from rest, exercise or recovery. Endothelial cell function, in terms of proliferation and wound-healing, was examined. To gain insight into the mechanism of interaction between exercise-derived MVs and endothelial cells, blockade studies were incorporated into the functional assays. MV surface proteins were degraded with trypsin and the interaction between Axl and Gas6 was inhibited with an anti-Axl antibody. Several mistakes were made within the course of this study, including incorrect preparation of the sodium citrate anticoagulant used for blood sample collection and possible microbial contamination of endothelial cell cultures. As such, the results of this study are inconclusive and further research is required to determine the effect of exercise-derived MVs on endothelial cell function and the pathways involved in this interaction. |
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