Effect of growth factors on human vascular endothelial cell prostacyclin production.
Prostacyclin (PGI2) is an antithrombotic factor, which may prevent the initiation and the complications of arteriosclerosis. The most important site of PGI2 production is the vascular endothelium, but little is known about how this process is regulated. In this connection, there is special interest in the roles of various growth factors released from platelets, macrophages, vascular smooth muscle cells, and the endothelial cells themselves. We investigated the effects of transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), and acidic and basic fibroblast growth factors (aFGF and bFGF) on the PGI2 production of cultured human umbilical vein endothelial cells by measuring the stable metabolite of PGI2, 6-keto-prostaglandin F1 alpha, by radioimmunoassay. TGF-beta induced dose- and time-dependent stimulation of PGI2 production. The lowest stimulatory concentration of TGF-beta was 0.1 ng/ml, and the maximal response, a 2.1-fold rise, was obtained with 1.0 ng/ml. The effect of TGF-beta lasted 48 hours and was blocked by inhibitors of transcription, translation, and cyclooxygenase. Maximal stimulation by TGF-beta was enhanced by epidermal growth factor. PDGF and bFGF had no effect on PGI2 production, but aFGF inhibited it. This is the first demonstration that TGF-beta enhances PGI2 production by human vascular cells, and this phenomenon may be part of negative feedback mechanisms that prevent thrombosis and arteriosclerosis.
Ristimäki
A
A
Children's Hospital, Helsinki, Finland.
Ylikorkala
O
O
Viinikka
L
L
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D015291:Transforming Growth Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D010982:Platelet-Derived Growth Factor; D003609:Dactinomycin; D015121:6-Ketoprostaglandin F1 alpha; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D003513:Cycloheximide; D011464:Epoprostenol; D007213:Indomethacin