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Heparin and acidic fibroblast growth factor interact to decrease prostacyclin synthesis in human endothelial cells by affecting both prostaglandin H synthase and prostacyclin synthase

✍ Scribed by Babette B. Weksler


Book ID
102883391
Publisher
John Wiley and Sons
Year
1990
Tongue
English
Weight
1009 KB
Volume
142
Category
Article
ISSN
0021-9541

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✦ Synopsis


Prostaglandin production by cultured human endothelial cells varies with growth conditions. We observed a marked diminution in both spontaneous and inducible production of prostacyclin (PGI,) by h u m a n umbilical vein and saphenous vein endothelial cells when they were cultured in the presence of the heparin-binding growth factor, acidic fibroblast growth factor (aFGF) and heparin, compared with PCI, production during culture in medium lacking these tactors. Decreased PGI, production was related to duration of exposure of the cells to aFGF and heparin and depended on the concentration of both substances. Heparin (1-100 Fgiml) strongly potentiated the effects of aFGF but had a limited and variable effect alone. The decrease in PGI, production correlated with a reduction in the cellular content of immunoreactive prostaglandin H synthase and prostacyclin synthase. Arachidonate deacylation was not decreased. In addition, the eicosanoid profile of endothelial cells was changed by exposure to aFGF and heparin. These studies indicate that heparin acts as a modulator of prostaglandin synthesi5 in endothelial cells through its interaction with aFCF, mediated by alterations in two key enzymes in the arachidonate metabolic pathway.