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Effects of Insulin-Like Growth Factor I and II on Prostaglandin Synthesis and Plasminogen Activator Activity in Human Umbilical Vein Endothelial Cells

Cattedra di Fisiopatologia della Riproduzione Umana (F.Mic., F.Min., M.O., G.L., M.F.G., B.P., R.A.) and Istituto Scientifico Internazionale "Paolo VI" (F.T.), Università Cattolica del Sacro Cuore, 00168 Rome, Italy; Dipartimento di Istologia ed Embriologia Medica (S.V., R.C.), Universitá degli Studi di Roma "La Sapienza", 00161 Rome, Italy; and Istituto di Ricerca "Associazione OASI Maria SS ONLUS" (A.T., A.L.), 94018 Troina (EN), Italy

Address all correspondence and requests for reprints to: Rosanna Apa, M.D., Cattedra di Fisiopatologia della Riproduzione Umana, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Roma, Italia. E-mail: krimisa{at}libero.it.

IGFs seem to contribute to the endothelial dysfunction observed in some vascular diseases. Because locally increased IGFs levels were detected in the preeclamptic fetoplacental unit, we hypothesized their involvement in the dysregulation of fibrinolysis and vascular tone typically observed in the fetoplacental compartment in this pregnancy disease. Therefore, in human umbilical vein endothelial cells (HUVECs), the potential effect of IGFs on the synthesis of plasminogen activators (PAs), PA inibitor-1 (PAI-1), and vasodilator and vasoconstrictor prostaglandins (PGs) was investigated. Moreover, in HUVECs treated with IGFs, the expression of cyclooxygenase (COX)-2, the rate-limiting enzyme in PG synthesis, was evaluated.

HUVECs were treated for 24 h with IGFs (1–100 ng/ml) or IL-1ß (0.1 ng/ml). PA, PAI-1, and COX-2 mRNA was determined by RT-PCR and PG release and PA activity by RIA and colorimetric assay, respectively.

We demonstrated an inhibition of urokinase-type PA activity and a 50% reduction of urokinase-type PA mRNA in HUVECs treated with IGFs. No effect was seen on PAI-1. Finally, both IGFs significantly decreased all PGs tested and COX-2 mRNA, whereas, as expected, IL-1ß had an opposite effect.

In conclusion, our results suggest for IGFs a potential involvement in the endothelial dysfunction observed in preeclamptic fetoplacental unit.

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