title: Tissue inhibitor of metalloproteinase-2 inhibits burn-induced derangements and hyperpermeability in microvascular endothelial cells.
abstract: BACKGROUND
  Burns induce microvascular hyperpermeability. We hypothesize that this occurs partly through an imbalance between matrix metalloproteinases (MMPs) and endogenous MMP inhibitors such as tissue inhibitors of metalloproteinases (TIMPs), and that such derangements can be attenuated with the use of TIMP-2.
  
  
  METHODS
  Rats underwent either sham or burn: serum and tissue were collected. Western blot was used to examine MMP-9 and TIMP-2 levels and MMP activity was assayed from lung tissue. Rat lung microvascular endothelial cells were used to assess monolayer permeability and evaluate the adherens junction proteins β-catenin, vascular endothelial cadherin and filamentous actin after exposure to burn serum ± TIMP-2.
  
  
  RESULTS
  Lung tissue from burn animals showed increased MMP activity, decreased levels of TIMP-2, and no difference in levels of active MMP-9 in burn vs control groups. Burn serum increased monolayer permeability, damaged adherens junction proteins, and incited actin stress fiber formation; TIMP-2 attenuated these derangements.
  
  
  CONCLUSIONS
  Burns may lower TIMP-2 levels and increase MMP activity and that TIMP-2 application in vitro may attenuate burn-induced hyperpermeability and decreases damage to endothelial structural proteins. These links warrant further investigation.
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott and White Health, 702 S.W. H.K. Dodgen Loop, Temple, TX, 76504, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Wiggins-Dohlvik
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott and White Health, 702 S.W. H.K. Dodgen Loop, Temple, TX, 76504, USA.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Oakley
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott and White Health, 702 S.W. H.K. Dodgen Loop, Temple, TX, 76504, USA.
authors.forename: Min Suk
authors.initials: MS
authors.lastname: Han
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott and White Health, 702 S.W. H.K. Dodgen Loop, Temple, TX, 76504, USA.
authors.forename: Hayden W
authors.initials: HW
authors.lastname: Stagg
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott and White Health, 702 S.W. H.K. Dodgen Loop, Temple, TX, 76504, USA.
authors.forename: Himakarnika
authors.initials: H
authors.lastname: Alluri
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott and White Health, 702 S.W. H.K. Dodgen Loop, Temple, TX, 76504, USA.
authors.forename: Chinchusha A
authors.initials: CA
authors.lastname: Shaji
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott and White Health, 702 S.W. H.K. Dodgen Loop, Temple, TX, 76504, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Davis
authors.affiliation: Department of Surgery, Texas A&M University Health Science Center College of Medicine and Baylor Scott and White Health, 702 S.W. H.K. Dodgen Loop, Temple, TX, 76504, USA. Electronic address: btharakan@sw.org.
authors.forename: Binu
authors.initials: B
authors.lastname: Tharakan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002056:Burns / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D055806:Microvessels / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D020011:Protective Agents; D019716:Tissue Inhibitor of Metalloproteinase-2; D020780:Matrix Metalloproteinase 9
keywords: Burn; Hyperpermeability; MMP; Shock; TIMP; Vascular