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Nitroglycerin (GTN) and the other organic nitrates are clinically useful in the management of ischemic cardiovascular diseases. However, research indicates that continuous nitrate therapy has a multitude of potentially adverse effects on the cardiovascular system. We conducted a study to characterize the effects of continuous GTN exposure on human vascular stem cells known as endothelial progenitor cells (EPCs), which are thought to be involved in cardiovascular homeostasis and repair. The results of this study indicate that continuous GTN therapy may negatively impact these cells, possibly leading to impaired neovascularization and endothelial regeneration. This study is the first to document effects of sustained GTN exposure on human progenitor cells, and illuminates a novel mechanism by which this compound may exert negative cardiovascular effects. Evidence of the potential for nitrate-induced cardiovascular toxicity is rapidly accumulating, and thus, it is time to investigate the long-term safety of these compounds in clinical practice.The function of SER-3, an orphan C. elegans GPCR with high sequence homology to biogenic amine receptors, was studied in transiently transfected HEK-293 cells. The expression of Flag-tagged SER-3 receptor in transfected cells was confirmed by western blot analysis of cell lysate and Flag-FITC immunofluorescence. Our functional studies, using cyclic AMP response element-dependent reporter expression, showed that SER-3 can be activated by octopamine through activation of CRE and AP1 signalling. The dose response studies showed that octopamine is more potent than dopamine and serotonin for activation of the SER-3 receptor in the CRE reporter system suggesting that SER-3 may act as an octopamine receptor in C. elegans. SER-3 expression was identified in various head and tail neurons in C. elegans.
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Nitroglycerin attenuates human endothelial progenitor cell function, differentiation and survival.
2006
in English
0494163828 9780494163825
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Source: Masters Abstracts International, Volume: 44-06, page: 2774.
Thesis (M.Sc.)--University of Toronto, 2006.
Electronic version licensed for access by U. of T. users.
ROBARTS MICROTEXT copy on microfiche.
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