(Hypertension. 2000;35:1307.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
8-Iso-Prostaglandin F2
Reduces Trophoblast Invasion and Matrix Metalloproteinase Activity
From the Institute for Nutrition Research, Faculty of Medicine (A.C.S., T.R., T.H., B.H.), and the Departments of Obstetrics and Gynecology, Aker University Hospital (A.C.S.) and National Hospital (T.H.), University of Oslo, Norway.
Correspondence to Anne Cathrine Staff, MD, Institute for Nutrition Research, Faculty of Medicine, Domus Medica, University of Oslo, PO Box 1046 Blindern, N-0316 Oslo, Norway. E-mail astaff{at}basalmed.uio.no
Abstract—Preeclampsia is a common
pregnancy complication in the latter half of gestation diagnosed by
hypertension and proteinuria. A key feature of preeclampsia is an
altered placentation with reduced trophoblast invasion. Normal
placentation requires controlled invasion of trophoblasts into the
maternal uterine wall, with secretion of specific proteolytic enzymes
able to degrade basement membranes and extracellular matrix, such as
the matrix metalloproteinases (MMPs). 8-Iso-prostaglandin
F2
(8-iso-PGF2) is a marker of oxidative
stress in vivo and is biologically active. We have recently reported an
elevated content of free 8-iso-PGF2 in preeclamptic
gestational tissue at delivery. Assuming an elevated level of
8-iso-PGF2 during the invasion period of the pregnancy,
we hypothesized that 8-iso-PGF2 could reduce invasion of
JAR cells, a choriocarcinoma cell line. We investigated JAR cell
invasion with 2 types of Transwell assays and demonstrated
that 8-iso-PGF2 (10 µmol/L) resulted in reduced
cell invasion in both the colorimetric and
radioactivity Transwell assays (P<0.01). Zymograms
revealed reduced MMP-2 and MMP-9 activity in conditioned media from JAR
cells incubated with 8-iso-PGF2 (10 µmol/L)
(P<0.02). 8-Iso-PGF2 (10 µmol/L)
also reduced the collagenase type IV activity in the
conditioned media of JAR cells (P=0.04). No effects on
MMP-2 and MMP-9 mRNA levels were observed after incubation with
8-iso-PGF2 (10 µmol/L), whereas protein levels
were significantly decreased (P<0.02), suggesting a
posttranscriptional regulation. We hypothesize a potential role for
8-iso-PGF2 in the reduced trophoblast invasion in
preeclampsia.
Key Words: preeclampsia • prostaglandins • gelatinases • oxidative stress • hypertension, pregnancy
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