TIMPs Expression as A Maternal Cell Free Plasma Biomarker of Severe Preeclampsia: A Case-Control Study.

OBJECTIVE: Preeclampsia (PE) is a pregnancy related disorder with prevalence of 6-7%. Insufficient trophoblastic invasion leads to incomplete remodeling of spiral arteries and consequent decrease in feto-placental perfusion. Altered placental expression of tissue inhibitors of matrix metalloproteinase (TIMPs) is considered to be involved in this process while the balance between matrix metalloproteinases (MMPs) and TIMPs contributes to remodeling of the placenta and uterine arteries by degradation and refurbishing of extracellular matrix (ECM). Therefore, TIMPs, fetal expression pattern was evaluated with the aim of its potential to be used as a determinant for the (early) detection of PE. MATERIALS AND METHODS: In this case-control study, cell free fetal RNA (cffRNA) released by placenta into the maternal blood was used to determine expression patterns of TIMP1, 2, 3 and 4 in the severe preeclamptic women in comparison with the normal pregnant women. Whole blood from 20 preeclamptic and 20 normal pregnant women in their 28-32 weeks of gestational age was collected. The second control group consisted of 20 normal pregnant women in either 14 or 28 weeks of gestation (each 10). cffRNA was extracted from plasma and real-time polymerase chain reaction (PCR) was done to determine the expression levels of TIMP1, 2, 3 and 4 genes. RESULTS: Statistical analysis of the results showed significant higher expression of TIMP1-4 in the preeclamptic women in comparison with the control group (P=0.029, 0.037, 0.037 and 0.049, respectively). Also, an increased level of TIMPs expression was observed by comparing 14 to 28 weeks of gestational age in the normal pregnant women in the second control group. CONCLUSION: An increased cffRNA expression level of TIMPs may be correlated with the intensity of placental vascular defect and may be used as a determinant of complicated pregnancies with severe preeclampsia.

Gene expression analysis of MMPs in women with preeclampsia using cell-free fetal RNA in maternal plasma.

OBJECTIVE: Nucleic acids released from the placenta into the mother's blood circulation system provide a valuable source of potential biomarkers for early detection of pregnancy complications such as preeclampsia (PE). PE affects nearly 5-10% of pregnancies worldwide and is a major contributor to the maternal and neonatal mortality and morbidity. It is known that altered placental expression of matrix metalloproteinases (MMPs) may cause shallow cytotrophoblastic invasion and ultimately lead to preeclampsia. The present study aimed to evaluate pattern of placental/fetal expression of the MMP family (MMP-2, MMP-9, MMP-14, MMP-15 and MMP-26) in preeclamptic women and compare it to normal pregnancies, using cell free fetal RNA (cff-RNA). METHODS: Blood samples were obtained from 20 pregnant women diagnosed with severe PE (28-32 weeks) and 40 control healthy pregnant women in two groups of either matched gestational age (N = 20) or 14 and 28 weeks pregnancies (each 10). cff-RNA was extracted from plasma, followed by reverse transcription of cff-RNA. Expression of MMP genes was measured using quantitative reverse transcription PCR (qRT-PCR). RESULTS: The expression levels of MMP-2, MMP-9 and MMP-15 were significantly increased, while MMP-14 expression level was significantly reduced and the expression of MMP-26 showed a relative increase in PE pregnancies compared to the control group. Additionally, increased level of MMPs expression was observed by comparing 14 and 28 weeks gestation age in normal pregnancy. CONCLUSION: Using cff-RNA, circulatory expression level of MMP-2, MMP-9, MMP-14 and MMP-15 were significantly altered in preeclampsia compared to normal pregnancies.