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

Abstract

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.

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

“…While MMP-2 genotypes and haplotypes are not linked with hypertensive disorders of pregnancy, MMP-2 genotypes and haplotypes are associated with significant alterations in plasma MMP-2 and TIMP-2 concentrations in preeclampsia. The increased MMP-2 concentrations in preeclampsia agree with results previously reported (Montagnana et al, 2009;Myers et al, 2005b;Narumiya et al, 2001). Although the increased TIMP-2 concentrations that we found in preeclampsia contrast with previous results (Montagnana et al, 2009), our findings align with similar findings reported in another cross-sectional study (Tayebjee et al, 2005).…”

“…The increased MMP-2 concentrations in preeclampsia agree with results previously reported (Montagnana et al, 2009;Myers et al, 2005b;Narumiya et al, 2001). Although the increased TIMP-2 concentrations that we found in preeclampsia contrast with previous results (Montagnana et al, 2009), our findings align with similar findings reported in another cross-sectional study (Tayebjee et al, 2005). It is possible that differences in the methods used to measure MMP-2 (ELISA vs. zymography), or differences between patients or gestational ages at sampling may explain the inconsistencies between studies (Montagnana et al, 2009; Myers et al, 2005b).…”

“…Impaired MMP activity is involved in many clinical conditions affecting the cardiovascular system including hypertensive disorders of pregnancy (Montagnana et al, 2009;Myers et al, 2005b;Narumiya et al, 2001;Palei et al, 2008;Tayebjee et al, 2005). Specifically, MMP-2 may be involved in uteroplacental artery remodeling and control of cytotrophoblastic invasion (Isaka et al, 2003;Shimonovitz et al, 1994).…”

Serum protein microarray analysis of patients with preeclampsia

“…The balance between MMPs and TIMPs is likely to play an important role in the remodeling of uterine arteries in pregnancy, and it may represent the means by which vasodilatation is maintained in later pregnancy (12). It has been confirmed that MMP-2 and TIMP-1 expression is significantly increased in preeclampsic patients (13,14). Changes in circulating levels of MMP-9, TIMP-1 and TIMP-2 have also been noted in gestational hypertensive patients (15).…”

The content of matrix metalloproteinase-12 in pregnancy complicated by preeclampsia

“…В плаценте представлено множество изоформ ММП. Большое внимание исследователей уделяется ММП 2-го и 9-го ти-пов, показана их роль при беременности: они определяют ход имплантации, плацентации, влияют на инвазивную способность трофобла-ста в эндометрии [9][10][11]. Относительно ММП-12 в литературе имеются единичные исследова-ния, посвященные изучению при беременно-сти [12][13][14].…”