title: Imbalance between matrix metalloproteinases (MMP-9 and MMP-2) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in acute respiratory distress syndrome patients.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) are known to be involved in degradation of extracellular matrix. We aimed to assess the role of MMPs and their natural inhibitors (TIMPs) in the genesis and the evolution of acute respiratory distress syndrome (ARDS).
  
  
  METHODS
  Prospective, clinical study.
  
  
  METHODS
  Intensive care unit of a university hospital.
  
  
  METHODS
  Twenty-one patients were assigned to three different groups: Group 1 patients developed ARDS that rapidly resolved in <4 days; Group 2 patients developed ARDS lasting >8 days; Group 3 (control group) patients had clinical criteria for hospital-acquired pneumonia without ARDS.
  
  
  METHODS
  Bronchoalveolar lavages were performed on day 0 of the onset of ARDS and on days 4, 8, and 12 for unresolving ARDS. For group 3, the bronchoalveolar lavages were performed on day 0 of the pneumonia. On these bronchoalveolar lavage fluids, we measured the amount of MMP-9 and -2 and their inhibitors TIMP-1 and -2.
  
  
  RESULTS
  The amount of MMP-9 measured by enzyme-linked immunosorbent assay was significantly lower in the bronchoalveolar lavages from patients with ARDS (group 1 and group 2) compared with the control group (p <.01) throughout the study. The ratio MMP-9/TIMP-1 was also significantly smaller and was less than one in the two ARDS groups (p <.05) compared with the control group (group 3), where this ratio was greater than one. In the second bronchoalveolar lavages, this ratio was greater than one only in the ARDS group that rapidly resolved (group 1), whereas it stayed less than one when the ARDS was lasting (group 2). Concerning the quantity of MMP-2 and the ratio MMP-2/TIMP-2, there was no statistical difference between the three groups throughout the study. Using zymography, there was no significant difference in the amounts of active and latent MMP-9 between the three groups. Moreover, no significant difference in the quantity of latent and active MMP-2 in the three groups was noted.
  
  
  CONCLUSIONS
  These results suggest that the MMP-9 level and MMP-9/TIMP-1 ratio play a role in the pathogenesis of ARDS and, namely, the imbalance between MMP-9 and TIMP-1 would participate in airway remodeling leading to either short- or long-course ARDS. The ratio MMP-9/TIMP-1 could be a predictive factor of the ARDS evolution.
authors.affiliation: INSERM U456, Université de Rennes, Service de Réanimation Chirurgicale, CHU de Rennes, Hôpital de Pontchaillou, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lanchou
authors.forename: Marianne
authors.initials: M
authors.lastname: Corbel
authors.forename: Michèle
authors.initials: M
authors.lastname: Tanguy
authors.forename: Noëlla
authors.initials: N
authors.lastname: Germain
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Boichot
authors.forename: Nathalie
authors.initials: N
authors.lastname: Theret
authors.forename: Bruno
authors.initials: B
authors.lastname: Clement
authors.forename: Vincent
authors.initials: V
authors.lastname: Lagente
authors.forename: Yannick
authors.initials: Y
authors.lastname: Malledant
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000201:enzymology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9