Circulating levels of tissue inhibitor of metalloproteinase 3, a protein with inhibitory effects on angiogenesis, are increased in pre-eclampsia.

Abstract

To assess and compare circulating tissue inhibitor of metalloproteinase 3 (TIMP-3) concentrations between women with pre-eclampsia and healthy pregnant women. We also aimed to determine the relationships between circulating TIMP-3 and matrix metalloproteinase 2 (MMP-2), MMP-9, TIMP-1, and TIMP-2 concentrations in pre-eclampsia. A primary case-control study included patients with pre-eclampsia (n= 219) and gestational hypertension (n= 118), healthy pregnant women (n= 214), and non-pregnant women (n= 66), and a replication case-control study included patients with pre-eclampsia (n= 177) and healthy pregnant women (n= 124), all from southeastern Brazil. Plasma TIMP-3, MMP-2, MMP-9, TIMP-1, and TIMP-2 concentrations were assessed using commercially available enzyme-linked immunosorbent assay kits, and the relationships between them were analyzed using Spearman's correlation. In our primary study, patients with pre-eclampsia and gestational hypertension exhibited increased TIMP-3 concentrations compared with healthy pregnant women (both P< 0.0001) and non-pregnant women (both P< 0.001). These findings were confirmed in the replication study, showing elevated TIMP-3 concentrations in women with pre-eclampsia versus healthy pregnant women (P< 0.001). We found no difference in TIMP-3 concentrations between early-onset and late-onset pre-eclampsia. Moreover, TIMP-3 concentrations were significantly correlated with plasma concentrations of TIMP-1 (r= 0.2333; P= 0.0086) and MMP-2 (r= 0.2159; P= 0.0156) in pre-eclampsia. Circulating TIMP-3 concentration is increased in women with pre-eclampsia compared with healthy pregnant women, and it is positively correlated with plasma MMP-2 and TIMP-1 concentrations in pre-eclampsia.