Altered subcellular distribution of cadherin-5 in endothelial cells caused by the serum of pre-eclamptic patients.
The main clinical features of pre-eclampsia are oedema and vascular leakage. Cadherin-5 mediates endothelial cell-cell contact in the vascular endothelium and may regulate permeability as a vascular function. Therefore, we addressed the question of whether pre-eclampsia alters cadherin-5 expression and intracellular distribution. Confluent human umbilical vein endothelial cells (HUVEC) were incubated with 20% serum from patients with pre-eclampsia (n = 18), haemolysis-elevated liver enzymes-low platelet syndrome (HELLP) (n = 12), pregnancy-induced hypertension (PIH) (n = 18) or normal pregnancy (n = 10). After incubation with sera from patients with pre-eclampsia, immunostaining analyses showed cadherin-5 accumulation in vesicular and tubular structures of the Golgi apparatus. Immunoblot analyses of HUVEC after pre-eclampsia serum incubation showed an increase of the stable form of cadherin-5 while degradation products decreased. Degradation of cadherin-5 takes place at the cell membrane, so this decrease may be due to a decrease of cadherin-5 in the cell membrane. The accumulation of cadherin-5 in the vesicular and tubular structures of the Golgi apparatus indicates that targeting of cadherin-5 to the plasma membrane could be disrupted. We suggest that intracellular retention of cadherin-5 caused by serum factors in patients with pre-eclampsia may decrease the number of adhesion complexes in the cell membrane, thereby contributing to endothelial dysfunction.
Groten
T
T
Department of Obstetrics and Gynecology, University of Ulm, Department of Biochemistry, University of Ulm, Germany. tanja.groten@medizin.uni-ulm.de
Kreienberg
R
R
Fialka
I
I
Huber
L
L
Wedlich
D
D
D000328:Adult; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D017359:HELLP Syndrome / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D000099152:Cadherin 5