Altered expression of gelatinase and surface-associated plasminogen activator activity by trophoblast cells isolated from placentas of preeclamptic patients

Abstract

OBJECTIVE: This study compared in vitro degradative properties of trophoblasts isolated from placentas of preeclamptic patients with those of trophoblasts isolated from placentas of patients with uncomplicated pregnancies. Specifically, the expression of gelatinases, plasminogen activators, and plasminogen activator inhibitor type 1 by these cells was examined. STUDY DESIGN: Gelatinase and plasminogen activator secretion were determined by zymography, whereas antigenic levels of urinary-type plasminogen activator and plasminogen activator inhibitor type 1 in culture-conditioned medium were determined by enzyme-linked immunosorbent assay. We also evaluated expression of cell-surface plasminogen activator activity with a sensitive assay that uses the fluorescent plasmin substrate H-D-Val-Leu-Lys-7-amino-4-methylcoumarin. RESULTS: Cells from both normal and preeclamptic placentas secreted variable levels of gelatinase, of which the most predominant was matrix metalloproteinase-9 (gelatinase B). In 60% of the media conditioned by preeclamptic cells the matrix metalloproteinase-9 present was exclusively of a higher molecular weight (>92 kd) than the predominant enzyme secreted by trophoblasts isolated from normal placentas. Incubation of the preeclamptic cell culture-conditioned media with p-aminophenylmercuric acetate, an activator of metalloproteinases, resulted in a decrease in the apparent molecular weight of the enzyme, indicating that most of the matrix metalloproteinase-9 contained in these samples was in the inactive form. Although trophoblasts from normal and preeclamptic placentas secreted similar amounts of urinary-type plasminogen activator and plasminogen activator inhibitor type 1, the latter cells expressed significantly less (p < 0.001) cell surface plasminogen activator activity. CONCLUSION: These results suggest that abnormal uteroplacental blood flow in preeclampsia (as a result of either shallow invasiveness of the uterine arteries or excessive fibrin deposition within the intervillous spaces) might result from altered expression of active proteinases by trophoblasts. (Am J Obstet Gynecol 1996;175:555-62.)