Serum from preeclamptic women induces vascular cell adhesion molecule-1 expression on human endothelial cells in vitro: a possible role of increased circulating levels of free fatty acids.
OBJECTIVE
The object was to determine whether serum from preeclamptic women induces expression of vascular cell adhesion molecule-1 on cultured endothelial cells.


METHODS
Endothelial cells were incubated with medium containing 20% serum (volume/volume) either from women with preeclampsia (n = 15) or from women with normal pregnancies (n = 15) matched for maternal age, gestational age, and parity. A further matched set of samples (n = 10) was exposed to endothelial cells that had previously been incubated in the presence or absence of vitamin E (40 micromol/L final concentration). Free fatty acids were determined in each sample. A mixture of free fatty acids (linoleic, oleic, and palmitic acids, 1:1:1) was added to serum from control subjects in increasing concentrations (70-280 micromol/L final concentration) to emulate preeclamptic serum and the preparation was exposed to endothelial cells. In each experiment vascular cell adhesion molecule-1 expression was determined after 16 hours of exposure by an enzyme-linked immunosorbent assay technique performed on the cell monolayer.


RESULTS
Preeclamptic serum had higher levels of free fatty acids than did that of control subjects (0.71 mmol/L, 95% confidence level 0.5-0.93, vs 0.36 mmol/L, 95% confidence level 0.28-0.43). There was a statistically significant increase in vascular cell adhesion molecule-1 expression on the endothelial cells exposed to preeclamptic serum compared with those exposed to control serum (optical density 0.17 vs 0.11). Vitamin E reduced the vascular cell adhesion molecule-1 expression of endothelial cells exposed both to preeclamptic and to control serum samples in a nonspecific manner. Addition of free fatty acids to normal pregnancy serum to mimic the effect of preeclampsia resulted in increased expression of vascular cell adhesion molecule-1 on the cells.


CONCLUSIONS
Preeclamptic serum induces vascular cell adhesion molecule-1 expression on human endothelial cells in vitro, an effect also produced by fatty acids. The elevated level of free fatty acids in women with preeclampsia may contribute to increased vascular cell adhesion molecule expression in vivo.
Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford, United Kingdom.
M J
MJ
Endresen
J M
JM
Morris
A C
AC
Nobrega
D
D
Buckley
E A
EA
Linton
C W
CW
Redman
D000328:Adult; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood* / Q000502:physiology*; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D012016:Reference Values; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology
D005230:Fatty Acids, Nonesterified; D019010:Vascular Cell Adhesion Molecule-1; D014810:Vitamin E