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Endothelial-cell permeability and protein kinase C in pre-eclampsia

Item Type:Article
Title:Endothelial-cell permeability and protein kinase C in pre-eclampsia
Creators Name:Haller, H. and Hempel, A. and Homuth, V. and Mandelkow, A. and Busjahn, A. and Maasch, C. and Drab, M. and Lindschau, C. and Juepner, A. and Vetter, K. and Dudenhausen, J. and Luft, F.C.
Abstract:BACKGROUND: Oedema and vascular leakage play a part in the pathogenesis of pre-eclampsia. We tested the hypothesis that serum from pre-eclamptic patients increases endothelial-cell permeability and examined possible signal-transduction pathways. METHODS: We studied eight patients with pre-eclampsia, eight normotensive pregnant women, eight non-pregnant women, five pregnant patients with pre-existing hypertension, and four hypertensive non-pregnant women. Cultured human umbilical-vein endothelial-cell monolayers were used and permeability was measured by albumin flux. The part played by protein kinase C (PKC) signalling was examined by down-regulation with phorbol ester and with the inhibitors Goe 6976 and staurosporine. PKC isoforms were assessed by western blot and confocal microscopy. Antisense oligodesoxynucleotides (ODN) were used to test for specific PKC isoforms. FINDINGS: Serum from pre-eclamptic women increased endothelial permeability significantly (by 100%, p<0.01). The change in permeability decreased rapidly after delivery. Serum from normotensive pregnant women and non-pregnant women had no effect. Permeability was not influenced by serum from patients with essential hypertension or pregnant patients with pre-existing hypertension. Serum from pre-eclamptic patients induced a translocation of PKC isoforms alpha and epsilon within the cells. Goe 6976 and staurosporine (10(-8) mol/L) inhibited the increase in permeability induced by serum from pre-eclamptic patients. Down-regulation of PKC alpha and, to a lesser extent, PKC epsilon by antisense ODN also inhibited the pre-eclampsia-induced permeability increase. INTERPRETATION: Serum from pre-eclamptic patients contains a factor or factors that increase endothelial-cell permeability. The effect of pre-eclamptic serum may be mediated by PKC alpha and epsilon.
Keywords:Cell Membrane Permeability, Vascular Endothelium, Isoenzymes, Pre-Eclampsia, Pregnancy, Protein Kinase C, Signal Transduction
Source:Lancet
ISSN:0140-6736
Publisher:Lancet (U.K.)
Volume:351
Number:9107
Page Range:945-949
Date:28 March 1998
Official Publication:https://doi.org/10.1016/S0140-6736(05)60605-8
PubMed:View item in PubMed

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