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

Area of Science:

• Obstetrics and Gynecology
• Vascular Biology
• Cell Signaling

Background:

• Pre-eclampsia is characterized by edema and vascular leakage.
• The role of endothelial cell permeability in pre-eclampsia pathogenesis is under investigation.
• Potential serum factors and signaling pathways involved in pre-eclampsia require elucidation.

Purpose of the Study:

• To test the hypothesis that serum from pre-eclamptic patients increases endothelial cell permeability.
• To investigate the signal-transduction pathways involved in this process, particularly protein kinase C (PKC).

Main Methods:

• Studied serum effects on cultured human umbilical vein endothelial cells from various patient groups.
• Measured endothelial permeability using albumin flux assays.
• Investigated protein kinase C (PKC) signaling via inhibitors, down-regulation with phorbol ester, western blot, confocal microscopy, and antisense oligodeoxynucleotides (ODN).

Main Results:

• Serum from pre-eclamptic women significantly increased endothelial permeability by 100% (p<0.01), with rapid normalization post-delivery.
• Serum from normotensive pregnant and non-pregnant women, or those with essential hypertension, had no effect.
• Pre-eclamptic serum induced translocation of PKC alpha and epsilon, and inhibition of PKC signaling pathways (using Goe 6976, staurosporine, or antisense ODN) reduced the permeability increase.

Conclusions:

• Serum from pre-eclamptic patients contains factors that elevate endothelial cell permeability.
• Protein kinase C (PKC) alpha and epsilon signaling pathways are likely mediators of the increased vascular permeability observed in pre-eclampsia.