title: Imbalances between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in maternal serum during preterm labor.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) are involved in remodeling of the extracellular matrix (ECM) during pregnancy and parturition. Aberrant ECM degradation by MMPs or an imbalance between MMPs and their tissue inhibitors (TIMPs) have been implicated in the pathogenesis of preterm labor, however few studies have investigated MMPs or TIMPs in maternal serum. Therefore, the purpose of this study was to determine serum concentrations of MMP-3, MMP-9 and all four TIMPs as well as MMP:TIMP ratios during term and preterm labor.
  
  
  METHODS
  A case control study with 166 singleton pregnancies, divided into four groups: (1) women with preterm birth, delivering before 34 weeks (PTB); (2) gestational age (GA) matched controls, not in preterm labor; (3) women at term in labor and (4) at term not in labor. MMP and TIMP concentrations were measured using Luminex technology.
  
  
  RESULTS
  MMP-9 and TIMP-4 concentrations were higher in women with PTB vs. GA matched controls (resp. p = 0.01 and p<0.001). An increase in MMP-9:TIMP-1 and MMP-9:TIMP-2 ratio was observed in women with PTB compared to GA matched controls (resp. p = 0.02 and p<0.001) as well as compared to women at term in labor (resp. p = 0.006 and p<0.001). Multiple regression results with groups recoded as three key covariates showed significantly higher MMP-9 concentrations, higher MMP-9:TIMP-1 and MMP-9:TIMP-2 ratios and lower TIMP-1 and -2 concentrations for preterm labor. Significantly higher MMP-9 and TIMP-4 concentrations and MMP-9:TIMP-2 ratios were observed for labor.
  
  
  CONCLUSIONS
  Serum MMP-9:TIMP-1 and MMP-9:TIMP-2 balances are tilting in favor of gelatinolysis during preterm labor. TIMP-1 and -2 concentrations were lower in preterm gestation, irrespective of labor, while TIMP-4 concentrations were raised in labor. These observations suggest that aberrant serum expression of MMP:TIMP ratios and TIMPs reflect pregnancy and labor status, providing a far less invasive method to determine enzymes essential in ECM remodeling during pregnancy and parturition.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. inge.tency@ugent.be
authors.forename: Inge
authors.initials: I
authors.lastname: Tency
authors.forename: Hans
authors.initials: H
authors.lastname: Verstraelen
authors.forename: Ivo
authors.initials: I
authors.lastname: Kroes
authors.forename: Gabriële
authors.initials: G
authors.lastname: Holtappels
authors.forename: Bruno
authors.initials: B
authors.lastname: Verhasselt
authors.forename: Mario
authors.initials: M
authors.lastname: Vaneechoutte
authors.forename: Rita
authors.initials: R
authors.lastname: Verhelst
authors.forename: Marleen
authors.initials: M
authors.lastname: Temmerman
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000097:blood* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000097:blood* / Q000201:enzymology / Q000378:metabolism; D036801:Parturition / Q000097:blood / Q000378:metabolism; D011247:Pregnancy; D011446:Prospective Studies; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood* / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood* / Q000378:metabolism; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C560823:TIMP2 protein, human