Evaluation of metalloproteinases 2 and 9 and their inhibitors in physiologic and pre-eclamptic pregnancy.

Matrix metalloproteinases (MMPs) are a family of zinc and calcium-dependent endopeptidases involved in remodeling and physiological homeostasis of extracellular matrix (ECM). The metalloproteinases activity is predominantly modulated by specific tissue inhibitors of matrix metalloproteinases (TIMPs). The balance between MMPs and TIMPs is likely to play an important role in remodeling uterine arteries in pregnancy, and it may represent means by which vasodilatation is maintained in later pregnancy. Moreover, increased levels of MMPs and in particular MMP-2 play a role in the vascular alterations induced by hypertension. The aim of this study was the evaluation of MMP-2 and -9, along with their inhibitors TIMP-1 and -2, in pre-eclamptic women compared with normotensive pregnancy and non-pregnant women. Fourteen pre-eclamptic women were compared with 37 normotensive women in different gestational age and 21 non-pregnant women. Multiplexed sandwich enzyme-linked immunosorbent assay was used to measure MMPs and TIMPs simultaneously. MMP-2 levels were significantly higher in pre-eclamptic women vs. both non-pregnant and physiologic pregnant women. MMP-9 concentrations were significantly higher in physiologic pregnant vs. non-pregnant women. The serum levels of TIMP-1 were significantly higher in pre-eclamptic vs. both non-pregnant and physiologic pregnant women. TIMP-2 values were higher in physiologic pregnant women and pre-eclamptic women vs. non-pregnant women. A positive correlation between MMP-9 values and gestational age was observed in normal pregnant women. Results of the present investigation confirm that MMP-2 and TIMP-1 values are significantly higher in preeclampsia. We confirm that the modification of the fine balance between MMPs and their inhibitors plays a greater role in the structural and functional vascular changes of women with complicated pregnancies. (c) 2009 Wiley-Liss, Inc.