MMP-2 Levels are Elevated in the Plasma of Women Who Subsequently Develop Preeclampsia

Myers, Jenny; Merchant, Shaila J.; Macleod, Maureen; Mires, Gary; Baker, Philip N.; Davidge, Sandra T.

doi:10.1081/prg-200059836

Cited by 94 publications

(89 citation statements)

References 28 publications

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“…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).…”

Section: Discussionsupporting

confidence: 93%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Palei

Sandrim

Amaral

et al. 2012

Experimental and Molecular Pathology

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

Palei

Sandrim

Amaral

et al. 2012

Experimental and Molecular Pathology

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“…Hence, these factors might be contributing to poor migration and proliferation of the endothelial cells and poor development of new blood vessels. The observed high expression of MMP2 in maternal blood in preeclampsia is consistent with the documented high level of MMP2 in preeclamptic plasma (Myers et al 2005) and might have a role in regulating vascular tone, as highlighted by a recent study that suggested the role of MMP1 expression in vasoconstriction (Mousa et al 2012). Consistent with our results, high levels of TIMP1 and TIMP2 have been demonstrated in preeclamptic endothelial cells (Merchant et al 2004).…”

Section: Discussionsupporting

confidence: 80%

Imbalance between matrix metalloproteinases and their tissue inhibitors in preeclampsia and gestational trophoblastic diseases

Rahat¹,

Sharma²,

Bagga³

et al. 2016

Reproduction

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The invasion cascade exhibited by placental trophoblasts and cancerous cells bears many similarities, and it is attributed to extracellular matrix degradation mediated by matrix metalloproteinases (MMPs). Although proper and controlled invasion by trophoblasts into the maternal uterus is an essential requirement for maintenance of normal pregnancy, any abnormality in this phenomenon results in the development of invasion-related disorders such as gestational trophoblastic diseases (GTDs) and preeclampsia. We studied the epigenetic basis of differential expression of two placental MMPs (MMP2 and MMP9) and tissue inhibitors of metalloproteinases (TIMP2 and TIMP1) during normal gestation and invasion-related disorders, i.e., preeclampsia and GTDs. Our study suggests the association of H3K9/27me3 with differential expression of these MMPs and their inhibitors, which regulate the placental invasion during normal pregnancy, whereas no role of CpG methylation was observed in the differential expression of MMPs/TIMPs. Further, development of GTDs was associated with abnormally higher expression of these MMPs and lower levels of their inhibitors, whereas the reverse trends were observed for MMPs and their TIMPs in case of preeclampsia, in association with abnormal changes in H3K9/27me3. These results suggest the involvement of higher levels of MMPs in an aggressive invasive behavior depicted by GTDs, whereas lower levels of these MMPs in shallow and poor invasive phenotype associated with preeclampsia. Thus, our study shows the significance of a proper balance regulated by histone trimethylation between differential expression of MMPs and their TIMPs for maintaining normal pregnancy and its deregulation as a contributing factor for pathogenesis of invasive disorders during pregnancy.

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“…An imbalance in the MMP-2/TIMP-1 ratio has been found in women who develop preeclampsia. 44 Thus, up-regulation of Nodal and ALK7 may contribute to the pathogenesis of preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

Nodal Signals through Activin Receptor-Like Kinase 7 to Inhibit Trophoblast Migration and Invasion

Nadeem

Munir

et al. 2011

The American Journal of Pathology

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Trophoblast cell invasion into the uterus is an essential process for successful pregnancy, and shallow invasion of trophoblasts into the maternal decidua is linked to preeclampsia. We have reported that Nodal, a member of the transforming growth factor-␤ superfamily, acts through activin receptor-like kinase 7 (ALK7) to inhibit trophoblast proliferation and to induce apoptosis. In this study, we examined the spatial and temporal expression patterns of Nodal and ALK7 in human placenta from normal and preeclamptic pregnancies and investigated whether Nodal regulated trophoblast migration and invasion. Nodal and ALK7 were detected in villous and extravillous trophoblast cell populations in early gestation, and their levels were strongly up-regulated in preeclamptic placenta. Overexpression of Nodal or constitutively active ALK7 decreased cell migration and invasion, whereas knockdown of Nodal and ALK7 had the opposite effects. In placental explant culture, treatment with Nodal inhibited trophoblast outgrowth, whereas Nodal small-interfering RNA strongly induced the expansion of explants and the migration of extravillous trophoblast cells. Nodal stimulated the secretion of tissue inhibitor of metalloproteinase-1 and inhibited matrix metalloproteinase (MMP)-2 and MMP-9 activity. These findings suggest that the Nodal/ALK7 pathway plays important roles in human placentation and that its abnormal signaling may contribute to the development of preeclampsia.

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MMP-2 Levels are Elevated in the Plasma of Women Who Subsequently Develop Preeclampsia

Abstract: At all three gestational time points an imbalance in the MMP-2:TIMP-1 ratio was found in patients who subsequently developed preeclampsia. We speculate that increased net MMP-2 activity may contribute to the endothelial dysfunction that is central to the pathophysiology of preeclampsia.

Cited by 94 publications

References 28 publications

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

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

Imbalance between matrix metalloproteinases and their tissue inhibitors in preeclampsia and gestational trophoblastic diseases

Nodal Signals through Activin Receptor-Like Kinase 7 to Inhibit Trophoblast Migration and Invasion

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