Placental Expression of Vasoactive Agents and Tissue Factor in Pre-Eclamptic and Clyocosporine Treated Kidney Transplant Mothers

Abstract

We studied the Endothelin-1 (ET-1)/Nitric Oxide Synthase (NOS) balance system,which is one of the most important systems in the regulation of the blood flow in several organs, in the placenta and in the decidua in normal and pre-eclamptic women. Since cyclosporine (CsA) has the potential to affect fetal growth and maternal state, through the modulation of ET-1 and NO synthesis,we compared these data with those obtained from transplanted women. Eleven CsAtreated female kidney transplant recipients (Tx), without fetal growth restriction and/or PE, and 12 PE, non transplanted,women were recruited. Fourteen normal pregnancies served as controls. Placental expression of ET-1 was evaluated by in situ hybridization,NO synthase (NOS) by NADPH-diaphorase staining and in situ hybridization. Both PE and Tx showed a marked reduction of NADPH-diaphorase staining, as weIl as of endothelial constitutive NOS (ecNOS) mRNA, in the syncytiotrophoblast layer of all villi, whereas the expression of inducible NOS was unchanged.Normal placenta showed a strong positive signal of ET-1 along the endothelium of utero-placental arteries within the basal plate which was markedly increased only in the decidua of Tx.Thus,Tx patients showed the mean relevant alteration of ET-1/ecNOS balance, in spite of the Iack of any alteration of fetal growth and maternal renal function.We further explored the state of activation of placental endothelial cells, evaluating Tissue Factor (TF) gene expression.TF was strikingly increased only in PE patients,where it is localized in the endothelial cells, as weII as in the cytotrophoblast invading the basal decidua. The modification of ET-1/ecNOS vasoactive balance, as elicited by CsA, is unable to account for the major features of the preeclamptic state. In the same patients we compared the preceding results with the uterine and umbilical Doppler velocimetry.We found that all Tx patients showed normal umbilical artery blood flow velocimetry, all but one displayed a normal pattern of uterine artery waveforms.Our studies witness that the ET-1/NOS balance is unable to lead to the modifications of Doppler impedance in the umbilical and uterine arteries.