Altered Maternal Serum Matrix Metalloproteinases MMP-2, MMP-3, MMP-9, and MMP-13 in Severe Early- and Late-Onset Preeclampsia

Abstract

Objective The aim of this study was to determine whether maternal serum matrix metalloproteinases 2, 3, 9, and 13 levels differ in early- and late-onset preeclampsia and uncomplicated pregnancies. Patients and Methods The study was carried out in 125 pregnant women (29 with early-onset preeclampsia; 31 preeclamptic patients with late-onset preeclampsia; and 65 healthy pregnant controls). Levels of MMP-2, MMP-3, MMP-9, and MMP-13 were measured in the maternal serum using an enzyme-linked immunosorbent assay. Results Maternal serum MMP-2 levels in both the groups of preeclamptic women were significantly higher than those in the controls. Levels of MMP-3 were significantly higher in preeclamptic patients with early-onset disease; however, the MMP-3 levels in patients with late-onset preeclampsia were similar to those observed in the control subjects. MMP-9 levels were lower whereas the levels of MMP-13 were higher in both preeclamptic groups of pregnant women than in the healthy controls, but these differences were statistically insignificant. Conclusions One important finding of the present study was that MMP-3 appears to be involved solely in early-onset preeclampsia, but not in late-onset preeclampsia. Higher levels of MMP-2 and MMP-13 and lower levels of MMP-9 seem to be related to both early- and late-onset severe preeclampsia.

The Serum Levels of Circulating Matrix Metalloproteinase MMP-9, MMP-2/TIMP-2 Complex and TIMP-1 do not Change Significantly During Normal Pregnancy.

“…Few studies have investigated MMPs or TIMPs in maternal serum. Lakowska [7] reported that decreased MMP-9 levels may be involved on pathological processes during pregnancy such as intrauterine growth restriction (IUGR) and preeclampsia, but the results are not matched on pregnancy week. On the other hand, during pregnancy the blood volume increases so that may mix the results.…”

Decidual leucocytes infiltrating human spiral arterioles are rich source of matrix metalloproteinases and degrade extracellular matrix in vitro and in situ

“…MMPs that were highly expressed in dNK cells and macrophages were also assessed in EVTs. MMP1, ‐3, ‐10 and ‐13 were included, as these MMPs are known to be important in pregnancy . Serial immunostaining of remodelling SpA demonstrated that vEVT express all the MMPs profiled, although with variable staining intensity (Figure ).…”

A Dysregulation of the Prolactin/Vasoinhibin Axis Appears to Contribute to Preeclampsia

“…Similar to this observation, MMP serum levels change during pregnancy. MMP-2 and MMP 3 levels are elevated in sera of pregnant women, although circulating MMP-9 level is lower than in the absence of pregnancy (39,40). Also, MMP-2 levels increase in PE amniotic fluid (40,41).…”

“…MMP-2 and MMP 3 levels are elevated in sera of pregnant women, although circulating MMP-9 level is lower than in the absence of pregnancy (39,40). Also, MMP-2 levels increase in PE amniotic fluid (40,41). These data show that both, substrates and enzymes needed for vasoinhibin generation, are higher in pregnancy Excessive generation of PRL-, PL-, and PGH-derived vasoinhibin isoforms in the placenta (19,47) Entering of placental vasoinhibin into the maternal circulation and into amniotic fluid (17)(18)(19) Reduced placental neovascularization, vasopermeability, and vasodilation, high maternal blood pressure, low birth weight (13,15,43) TABLE 3 | Causal inference between vasoinhibin dysregulation and preeclampsia: application of the 2015 Bradford Hill criteria (48).…”