Decreased expression of matrix metalloproteinase-1 in the maternal umbilical serum, trophoblasts and decidua leads to preeclampsia

Abstract

The aim of the present study was to explore the levels of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the maternal umbilical serum, placenta and decidua of patients with preeclampsia compared with those in normotensive pregnant females. A total of 73 pregnant females were recruited as the test subjects, including 43 inpatients with hypertensive disorders in pregnancy and 30 normal pregnant females as the control. The 43 inpatients with hypertensive disorders in pregnancy included 18 patients with gestational hypertension, nine with mild preeclampsia and 16 with severe preeclampsia. MMP-1 and TIMP-1 ELISA kits were used to determine the MMP-1 and TIMP-1 levels in the umbilical serum of the parturient following delivery. MMP-1 and TIMP-1 expressed in the placenta and decidua of the parturient following delivery were evaluated using immunohistochemistry. MMP-1 and TIMP-1 were mainly located in cytotrophoblasts and syncytiotrophoblasts in the placenta and decidua. The levels of MMP-1 in the umbilical serum of the normal, gestational hypertension, mild preeclampsia and severe preeclampsia groups were 294.33±11.53, 247.78±20.32, 177.67±12.63 and 124.68±15.41 pg/ml, respectively, and there were significant differences between each two groups (P<0.05). The positive expression rate of MMP-1 in the placenta and decidua of patients with hypertensive disorders in pregnancy was lower than that of the controls (P<0.01 and P<0.01, respectively). However, no significant difference was identified between each two groups with regard to the levels of TIMP-1 in the umbilical cord and the positive rates in the placenta and decidua (P>0.05). Reduced MMP-1 levels in the umbilical serum, placenta and decidua were observed in women who developed preeclampsia.

Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia

“…Measurements of TIMP-1 and -2 in the circulation and umbilical serum have shown increases or no change in PE versus Norm-Preg women (Montagnana et al, 2009; Deng et al, 2015; Eleuterio et al, 2015), while other studies have shown increases in TIMP-1 and -3 in PE patients (Zhu et al, 2014). The role of MMPs and TIMPs in modulating vascular function and the endothelial dysfunction associated with PE should be further examined in future studies.…”

“…MMP-1 is also expressed in cytotrophoblasts and syncytiotrophoblasts of the placenta and decidua and may play a role in trophoblast invasion. MMP-1 levels in the umbilical cord blood, placenta and decidua are lower in PE than Norm-Preg women, and the low levels of MMP-1 are in a positive correlation with the severity of the disease (Deng et al, 2015). …”

Decreased homodimerization and increased TIMP-1 complexation of uteroplacental and uterine arterial matrix metalloproteinase-9 during hypertension-in-pregnancy

“…Also, TIMPs are important endogenous modulators of MMPs activity [16, 18, 25, 88, 89]. Some studies have shown increases or no change in TIMP-1 and −2 in the circulation and umbilical cord serum of preeclamptic vs normal Preg women [16, 24, 90]. Other studies have shown increases in TIMP-1 and −3 in preeclamptic patients [91].…”

Cell-type specific activities of cytomegalovirus GPCR homologues

“…While preeclampsia has been linked to a decrease of MMP-1 expression in placenta, umbilical serum and decidua, choriocarcinoma has been linked to an increase expression of MMP-1 in extravillous trophoblast (Cohen et al, 2012;Deng et al, 2015;Vegh et al, 1999), suggesting that US28 MMP-1 phenotype may be more related to cell survival. In transfected HUVECs, detectable levels of MMP-1 and MMP-10 were recorded, consistent with previous data showing upregulation of these mRNA upon exposure to inflammatory stimuli (Montero et al, 2006).…”

“…decidua have been associated with both normal and abnormal pregnancies (Deng et al, 2015;Lockwood et al, 2014;Vegh et al, 1999;Xu et al, 2000). Here, concentration of nine MMP in the cell culture supernatant were analysed in two in vitro settings by Luminex assays.…”