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

Abstract

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.