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Prostacyclin signaling boosts NADPH oxidase 4 in the endothelium promoting cytoprotection and angiogenesis
Citation
Peshavariya, HM and Liu, GS and Chang, CWT and Jiang, F and Chan, EC and Dusting, GJ, Prostacyclin signaling boosts NADPH oxidase 4 in the endothelium promoting cytoprotection and angiogenesis, Antioxidants and Redox Signaling, 20, (17) pp. 2710-2725. ISSN 1523-0864 (2014) [Refereed Article]
Copyright Statement
Copyright 2014 Mary Ann Liebert, Inc.
DOI: doi:10.1089/ars.2013.5374
Abstract
Results: The selective and stable prostacyclin receptor (IP-R) agonist cicaprost increases the expression of Nox4 in human endothelial cells of several types, including endothelial progenitor cells. The elevation of cellular cyclic-AMP increased Nox4 expression and H2O2 production and prevented endothelial cell apoptosis. We delineate the intracellular signaling that promotes cytoprotection: Cicaprost acts via the IP-R/protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein pathway. Importantly, the up-regulation of Nox4 by cicaprost also enhanced endothelial cell proliferation, migration, and angiogenesis, with all effects being substantially decreased by Nox4 gene silencing. Finally, cicaprost enhanced the growth of blood vessels into subcutaneous sponges implanted in mice, an effect that was also blocked by Nox4 gene silencing.
Innovation: The prostacyclin analogue cicaprost induces Nox4 via IP receptor-cAMP/PKA/CREB pathway. The activation of this pathway protects endothelial cells and enhances pro-angiogenic activity both in vitro and in vivo.
Conclusion: Prostacyclin promotes the up-regulation of Nox4 in endothelial cells, which opens up a novel strategy that protects and enhances endothelial cell functions in cardiovascular disease, such as repair after myocardial infarction or other ischemic conditions.
Item Details
Item Type: | Refereed Article |
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Research Division: | Biomedical and Clinical Sciences |
Research Group: | Medical biotechnology |
Research Field: | Gene and molecular therapy |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Liu, GS (Associate Professor Guei-Sheung Liu) |
ID Code: | 120781 |
Year Published: | 2014 |
Web of Science® Times Cited: | 31 |
Deposited By: | Menzies Institute for Medical Research |
Deposited On: | 2017-08-30 |
Last Modified: | 2019-01-21 |
Downloads: | 0 |
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