Circulating Tissue Inhibitor of Metalloproteinase-4 levels are not a Predictor of Preeclampsia in the period between 20 and 25 Weeks of Gestation.

Marco Antonio Barbieri,Ana Carolina Palei,Heloisa Bettiol,Jackeline Machado,Ricardo Carvalho Cavalli,Valeria Cristina Sandrim,Viviane Cunha Cardoso

doi:10.1055/s-0038-1676056

Abstract

To evaluate whether the circulating level of tissue inhibitor of metalloproteinase-4 (TIMP-4) in the period between 20 and 25 weeks of gestation is a predictor of preeclampsia. We have performed a case-control study, nested in a prospective study cohort in Ribeirão Preto, in the state of São Paulo, Brazil. Of the 1,400 pregnant women evaluated between 20 and 25 weeks of gestation, 460 delivered in hospitals outside of our institution. Of the 940 pregnant women who completed the protocol, 30 developed preeclampsia. Healthy pregnant women (controls, n = 90) were randomly selected from the remaining 910 participants. From blood samples collected between 20 and 25 weeks of gestation, we performed a screening of 55 angiogenesis-related proteins in 4 cases and 4 controls. The protein TIMP-4 was the most differentially expressed between cases and controls. Therefore, we measured this protein in all cases (n = 30) and controls selected (n = 90). There were no differences in the plasma TIMP-4 levels of cases compared with controls (1,144 ± 263 versus 1,160 ± 362 pg/mL, respectively; p > 0.05). Plasma TIMP-4 levels were not altered at 20 to 25 weeks of gestation, before the manifestation of clinical symptoms; therefore, they are not good predictors of the development of preeclampsia.

Highlights

The early identification of pregnant women at high risk of developing preeclampsia is important, allowing the tracking and reduction of complications for the mother and the fetus
We performed a screening of 55 angiogenesis-related proteins in plasma collected in the period between 20 and 25 weeks of gestation from pregnant women who subsequently developed preeclampsia and from pregnant women who remained healthy until delivery
We decided to focus the subsequent experiments on tissue inhibitor of metalloproteinase-4 (TIMP-4) because, first, PIGF has been extensively explored in preeclampsia; secondly, heparin-binding epidermal growth factor (HB-EGF) was not detected in 2 samples of each group; and third, the variability of matrix metalloproteinases (MMPs)-9 levels was extremely high among the samples

Summary

Introduction

The early identification of pregnant women at high risk of developing preeclampsia is important, allowing the tracking and reduction of complications for the mother and the fetus. It is currently widely accepted that an antiangiogenic profile contributes to the pathophysiology of preeclampsia, few angiogenesis-based biomarkers have been explored in prediction studies, which include measurements of endostatin and of angiopoetin-1/2.7–9. We first screened 55 proteins related to angiogenesis in the plasma of pregnant women who subsequently developed preeclampsia (cases, n 1⁄4 4) compared with pregnant women who were healthy until delivery (control, n 1⁄4 4), collected at between 20 and 25 weeks of gestation. Our step was to validate the findings of the screening in a larger number of pregnant women (30 cases and 90 controls)

Methods

Results

Discussion

Conclusion