Selective augmentation of prostacyclin production by combined prostacyclin synthase and cyclooxygenase-1 gene transfer

Circulation
S K ShyueK K Wu

Abstract

We tested the hypothesis that combined cyclooxygenase-1 (COX-1) and prostacyclin synthase (PGIS) gene transfer selectively augments prostacyclin production without a concurrent overproduction of other prostanoids. ECV304 cells were transfected with bicistronic pCOX-1/PGIS versus pCOX-1 or pPGIS, and prostanoids were analyzed. Contrary to the high prostaglandin E2 synthesis in pCOX-1 transfected cells, selective prostacyclin formation was noted with bicistronic plasmid transfection. Next, we determined the optimal ratio of Ad-COX-1 to Ad-PGIS by transfecting human umbilical vein endothelial cells with various titers of these 2 adenoviral constructs and determined the level of protein expression and prostanoid synthesis. Our results show that optimal ratios of adenoviral titers to achieve a large prostacyclin augmentation without overproduction of prostaglandin E2 or F2alpha were 50 to 100 plaque forming units (pfu) of Ad-COX-1 to 50 pfu of Ad-PGIS per cell. A higher Ad-PGIS to Ad-COX-1 ratio caused a paradoxical decline in prostacyclin synthesis. Prostacyclin synthesis can be selectively augmented by cotransfecting endothelial cells with an optimal ratio of COX-1 to PGIS. Combined COX-1 and PGIS gene transfer has the potential f...Continue Reading

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Citations

Mar 20, 2003·Journal of Cardiac Surgery·Stephen J White, Andrew C Newby
Apr 22, 2006·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·S Moncada
Nov 6, 2007·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yu YunZhi Qiang Shen
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May 28, 2010·Journal of Cellular Biochemistry·Tzong-Shyuan LeeSong-Kun Shyue
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Apr 26, 2015·Prostaglandins & Other Lipid Mediators·Ling-yun ChuKenneth K Wu
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