Maternal Plasma Levels of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 as Predictive Biomarkers of Preeclampsia

Background: Preeclampsia (PE), a severe pregnancy complication, is a major contributor to maternal and perinatal morbidity and mortality worldwide. Matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) are implicated in the pathogenesis of PE. This study aimed to evaluate maternal plasma levels of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 in normal and preeclamptic pregnancies across gestational trimesters to assess their predictive value. Methods: This case-control study included a total of 138 pregnant women: 72 with normal pregnant women (controls) and 66 women diagnosed with PE, recruited at Hanoi Obstetrics and Gynecology Hospital between July 2022 and June 2024. In the second trimester (14–28 weeks), the PE and control groups included 14 and 18 women, respectively. In the third trimester (29–41 weeks), the study included 52 women with PE and 54 controls. Plasma concentrations of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 were measured using enzyme-linked immunosorbent assay (ELISA). Correlations between MMPs, TIMPs, MMP/TIMP ratios, and PE severity indices were analyzed using Spearman’s correlation. Receiver operating characteristic (ROC) analysis evaluated the diagnostic and predictive utility of these markers. Results: Maternal plasma levels of MMP-2 and TIMP-2 were significantly higher in the PE group compared to controls during both the second and third trimesters (p < 0.05). The MMP-2/TIMP-2 ratio was significantly lower in the PE group during the third trimester (p = 0.002). MMP-3 levels were markedly elevated in PE patients (p < 0.001) and were positively correlated with plasma creatinine and proteinuria. In contrast, MMP-9 levels were significantly reduced in the PE group across both trimesters (p < 0.05), whereas TIMP-1 levels showed no significant difference between groups. Notably, MMP-9 was strongly correlated with TIMP-1 in PE, and both markers correlated with systolic blood pressure (SBP). ROC curve analysis indicated the combination of MMP-2 and TIMP-2 as the best predictor of PE in the second trimester, while TIMP-2 was the most predictive marker in the third trimester. Conclusions: Elevated plasma MMP-2 and TIMP-2 levels, particularly in the second trimester, show potential as biomarkers for identifying patients at risk of PE. TIMP-2 appears promising for prediction in the third-trimester. These findings warrant further investigation for potential clinical application.