Heparin and acidic fibroblast growth factor interact to decrease prostacyclin synthesis in human endothelial cells by...

Area of Science:

• Endothelial cell biology
• Molecular endocrinology
• Biochemistry

Background:

• Prostaglandin production by endothelial cells is crucial for vascular homeostasis.
• Growth factors and extracellular matrix components can influence endothelial cell function.
• Acidic fibroblast growth factor (aFGF) and heparin are known to interact with endothelial cells.

Purpose of the Study:

• To investigate the effect of aFGF and heparin on prostaglandin production in human endothelial cells.
• To elucidate the mechanisms underlying changes in prostacyclin (PGI2) synthesis.

Main Methods:

• Culture of human umbilical vein and saphenous vein endothelial cells.
• Exposure to varying concentrations and durations of aFGF and heparin.
• Measurement of prostacyclin (PGI2) production.
• Quantification of prostaglandin H synthase and prostacyclin synthase levels.
• Analysis of eicosanoid profiles.

Main Results:

• aFGF and heparin markedly diminished both spontaneous and inducible PGI2 production.
• The reduction in PGI2 production was dose- and time-dependent.
• Heparin potentiated aFGF's effect, with limited independent activity.
• Decreased PGI2 correlated with reduced prostaglandin H synthase and prostacyclin synthase levels.
• Eicosanoid profiles were altered by aFGF and heparin exposure.

Conclusions:

• Heparin modulates prostaglandin synthesis in endothelial cells, particularly through its interaction with aFGF.
• This modulation is mediated by alterations in key enzymes of the arachidonate metabolic pathway, specifically prostaglandin H synthase and prostacyclin synthase.