ENDOTHELIAL-CELL PERMEABILITY AND PROTEIN-KINASE-C IN PREECLAMPSIA

Background Oedema and vascular leakage play a part in the pathogenesis of pre-eclampsia. We tested the hypothesis that serum from pre-eclamp tic increases endothelial-cell permeability and possible signal-transd uction pathways. Methods We studied eight patients with pre-eclampsia, eight normotensive pregnant women, eight non-pregnant women, five pre gnant patients with pre-existing hypertension, and four hypertensive n on-pregnant women, Cultured human umbilical-vein endothelial-cell mono layers were used and permeability was measured by albumin flux, The pa rt played by protein kinase C (PKC) signalling was examined by down-re gulation with phorbol ester and with the inhibitors Goe 6976 and staur osporine, PKC isoforms were assessed by western blot and confocal micr oscopy, Antisense oligodesoxynucleotides (ODN) were used to test for s pecific PKC isoforms. Findings Serum from pre-eclamptic women increase d endothelial permeability significantly (by 100%, p < 0.01). The chan ge in permeability decreased rapidly after delivery, Serum from normot ensive pregnant women and non-pregnant women had no effect, Permeabili ty was not influenced by serum from pateints with essential hypertensi on 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) in hibited the increase in permeability induced by serum from preeclampti c patients. Down-regulation of PKC alpha and, to a lesser extent, PKC epsilon by antisense ODN also inhibited the pre-eclampsia-induced perm eability increase. Interpretation Serum from pre-eclamptic patients co ntains a factor or factors that increase endothelial-cell permeability . The effect of pre-eclamptic serum may be mediated by PKC alpha and e psilon.