Degradation of fibronectin in association with vascular endothelial disruption in preeclampsia.
The objectives of this study were (1) To assess human umbilical cord vein endothelial cell (HUVEC) fibronectin (Fn) content and integrity in patients with preeclampsia and (2) to investigate the ability of Fn and Fn fragments (FnDP) to disrupt endothelial cell attachment to an Fn matrix through modulation of plasminogen activator activity. Intact Fn was released from normal cord veins, while Fn and FnDP (70 and 21 kd) were released from cord veins in culture from patients with severe preeclampsia. Factor VIII and Fn immunostaining of normal cord sections revealed endothelial integrity and low Fn content, while immunostaining of cord sections from patients with preeclampsia revealed a disrupted endothelium and high concentrations of Fn. Both intact Fn and FnDP isolated from patient plasma or prepared by plasmin digestion of pure Fn had no effect on chromium 51 release from HUVECs. These FnDP, but not intact Fn, stimulated HUVEC urokinase plasminogen activator production within 2 hours (p < 0.05) and caused a time- and concentration-dependent detachment and disruption of the HUVEC monolayers and HUVEC-mediated degradation of immobilized iodine 125-labeled Fn underneath the HUVEC monolayer (p < 0.02) after 2 hours. This 125I-labeled Fn release was enhanced by plasminogen and inhibited by aprotinin. Thus FnDP appear to cause endothelial cell disruption that may be due to plasmin generation in vitro.
de Jager
C A
CA
MRC-UCT Liver Research Centre, Department of Medicine, South Africa.
Shephard
E G
EG
Robson
S C
SC
Jaskiewicz
K
K
Froese
S
S
Anthony
J
J
Kirsch
R E
RE
D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005341:Fibrinolysin / Q000096:biosynthesis; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008858:Microscopy, Phase-Contrast; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
D005353:Fibronectins; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator