Nitroglycerin attenuates human endothelial progenitor cell function, differentiation and survival.

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Nitroglycerin attenuates human endothelial pr ...
Jonathan Michael Di Fabio
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December 15, 2009 | History

Nitroglycerin attenuates human endothelial progenitor cell function, differentiation and survival.

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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.

Publish Date
Language
English
Pages
131

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Book Details


Edition Notes

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.

The Physical Object

Pagination
131 leaves.
Number of pages
131

ID Numbers

Open Library
OL19215913M
ISBN 13
9780494163825

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December 15, 2009 Edited by WorkBot link works
October 21, 2008 Created by ImportBot Imported from University of Toronto MARC record.