Matrix metalloproteinase-2 is elevated in midtrimester amniotic fluid prior to the development of preeclampsia

Lavee, Michal; Goldman, Shlomit; Daniel-Spiegel, Etty; Shalev, Eliezer

doi:10.1186/1477-7827-7-85

Cited by 24 publications

(35 citation statements)

References 20 publications

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“…Also, mean amniotic TIMP-2 levels are higher in women who developed a hypertensive disorder compared to normotensive women (Lavee et al, 2009; Montagnana et al, 2009). A decrease in ECM remodeling could play a role in HELLP syndrome.…”

Section: Mmps In Pregnancy and Preeclampsiamentioning

confidence: 95%

“…A study enrolling 133 women showed no statistical difference in MMP-2 levels between patients with gestational HTN and normotensive controls (Lavee et al, 2009) or between PE and normotensive women (Galewska et al, 2008). Another study enrolling 83 pregnant women showed no difference in pro-MMP-2 levels (Palei et al, 2008).…”

Section: Mmps In Pregnancy and Preeclampsiamentioning

confidence: 96%

“…Higher levels of MMPs such as MMP-2 and lower levels of TIMPs have been shown in women with PE (Narumiya et al, 2001; Montagnana et al, 2009; Shokry et al, 2009) or who subsequently develop PE (Myers et al, 2005; Lavee et al, 2009). Increased MMP-2 activity may contribute to the endothelial dysfunction in PE (Myers et al, 2005).…”

Section: Mmps In Pregnancy and Preeclampsiamentioning

confidence: 99%

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Matrix Metalloproteinase Inhibitors as Investigative Tools in the Pathogenesis and Management of Vascular Disease

Benjamin

Khalil

2012

Experientia Supplementum

133

139

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Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade various components of the extracellular matrix (ECM). MMPs could also regulate the activity of several non-ECM bioactive substrates, and consequently affect different cellular functions. Members of the MMPs family include collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs and others. Pro-MMPs are cleaved into active MMPs, which in turn act on various substrates in the ECM and on the cell surface. MMPs play an important role in the regulation of numerous physiological processes including vascular remodeling and angiogenesis. MMPs may also be involved in vascular diseases such as hypertension, atherosclerosis, aortic aneurysm, and varicose veins. MMPs also play a role in the hemodynamic and vascular changes associated with pregnancy and preeclampsia. The role of MMPs is commonly assessed by measuring their gene expression, protein amount, and proteolyic activity using gel zymography. Because there are no specific activators of MMPs, MMP inhibitors are often used to investigate the role of MMPs in different physiologic processes and in the pathogenesis of specific diseases. MMP inhibitors include endogenous tissue inhibitors (TIMPs) and pharmacological inhibitors such as zinc chelators, doxycycline and marimastat. MMP inhibitors have been evaluated as diagnostic and therapeutic tools in cancer, autoimmune and cardiovascular disease. Although several MMP inhibitors have been synthesized and tested both experimentally and clinically, only on MMP inhibitor, i.e. doxycycline, is currently approved by the Food and Drug Administration. This is mainly due to the undesirable side effects of MMP inhibitors especially on the musculoskeletal system. While most experimental and clinical trials of MMP inhibitors have not demonstrated significant benefits, some trials still showed promising results. With the advent of new genetic and pharmacological tools, disease-specific MMP inhibitors with fewer undesirable effects are being developed and could be useful in the management of vascular disease.

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Section: Mmps In Pregnancy and Preeclampsiamentioning

confidence: 95%

Section: Mmps In Pregnancy and Preeclampsiamentioning

confidence: 96%

Section: Mmps In Pregnancy and Preeclampsiamentioning

confidence: 99%

See 1 more Smart Citation

Matrix Metalloproteinase Inhibitors as Investigative Tools in the Pathogenesis and Management of Vascular Disease

Benjamin

Khalil

2012

Experientia Supplementum

133

139

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“…Both have been found in amniotic fluid and the concentrations of both zymogen and inhibitor free active forms of MMP9 are elevated in the amniotic fluid of women with pPROM 133144;150-153 We have previously reported that amniotic fluid TIMP2 concentrations are lower in women with spontaneous labor (term and preterm), with intact or ruptured membranes, regardless of the microbial status of the amniotic cavity, than in women not in labor 133. A decrease in TIMP2 amniotic fluid concentration is thought to favor MMP activity promoting extracellular matrix degradation, which has been associated with labor 152.…”

Section: Commentmentioning

confidence: 99%

A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM)

Romero

Friel

Edwards

et al. 2010

American Journal of Obstetrics and Gynecology

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Objective-To determine whether maternal/fetal SNPs in candidate genes are associated with preterm prelabor rupture of membranes (pPROM).Study Design-A case-control study was conducted in patients with pPROM (225 mothers and 155 fetuses) and 599 mothers and 628 fetuses with a normal pregnancy; 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; FDR was used to correct for multiple testing (q*=0.15)].Results-1) A SNP in TIMP2 in mothers was significantly associated with pPROM(OR=2.12 95% CI [1.47-3.07], p = 0.000068), and this association remained significant after correction for multiple comparisons; 2) Haplotypes for COL4A3 in the mother were associated with pPROM (global p = 0.003); 3) Multilocus analysis identified a three locus model, which included maternal SNPs in COL1A2, DEFA5, and EDN1.Conclusion-DNA variants in a maternal gene involved in extracellular matrix metabolism doubled the risk of pPROM.

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“…MMP2 is a constitutive enzyme, while MMP9 is inducible in response to infection. 140 Both have been found in amniotic fluid [141][142][143][144][145] and the activity and concentration of MMP9 is increased in the amniotic fluid of women with preterm labor and intact membranes, as well as in women with preterm PROM. 141;143 We have previously reported that amniotic fluid TIMP2 concentrations are low in women with spontaneous labor (term and preterm), with intact or ruptured membranes, regardless of the microbial status of the amniotic cavity.…”

Section: Single Locus Analysis For Mothersmentioning

confidence: 99%

14: Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes

Romero¹,

Velez²,

Mazaki‐Tovi³

et al. 2009

American Journal of Obstetrics and Gynecology

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Objective-To determine whether maternal/fetal SNPs in candidate genes are associated with spontaneous preterm labor/delivery. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptStudy Design-A genetic association study was conducted in 223 mothers and 179 fetuses [preterm labor with intact membranes who delivered <37 weeks (PTB)], and 599 mothers and 628 fetuses (normal pregnancy): 190 candidate genes and 775 SNPs were studied. Single locus/ haplotype association analyses were performed; FDR was used to correct for multiple testing (q*=0.15)]. Results-1)The strongest single locus associations with PTB were IL6R (fetus: p=0.000148) and TIMP2 (mother: p=0.000197), remaining significant after correction for multiple comparisons; 2) Global haplotype analysis indicated an association between a fetal DNA variant in IGF2 and maternal COL4A3 (global p=0.004 and 0.007, respectively).Conclusion-A SNP involved in controlling fetal inflammation (IL6R) and DNA variants in maternal genes encoding for proteins involved in extracellular matrix biology approximately doubled the risk of PTB.

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Matrix metalloproteinase-2 is elevated in midtrimester amniotic fluid prior to the development of preeclampsia

Abstract: Higher amniotic fluid MMP-2 and TIMP-2 levels are found in women who eventually develop preeclampsia.

Cited by 24 publications

References 20 publications

Matrix Metalloproteinase Inhibitors as Investigative Tools in the Pathogenesis and Management of Vascular Disease

Matrix Metalloproteinase Inhibitors as Investigative Tools in the Pathogenesis and Management of Vascular Disease

A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM)

14: Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes

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