title: Differential regulation of MMP-2 in the gastrohepatic ligament of the gastroesophageal junction.
abstract: BACKGROUND
  Ligamentous attachments maintain the normal anatomic position of the gastroesophageal (GE) junction. Failure of these elastic ligaments through an alteration in collagen synthesis, deposition, and metabolism may be a primary etiology of hiatal hernia formation. Differential expression of zinc-dependent matrix metalloproteinases (MMPs) is largely responsible for collagen remodeling. The purpose of this study was to survey baseline levels of MMPs in supporting ligaments of the GE junction from patients without hiatal hernia.
  
  
  METHODS
  Following an institutional review board-approved protocol, plasma and tissue biopsies of the gastrohepatic ligament (GHL), gastrophrenic ligament (GPL), and phrenoesophageal ligament (PEL) were obtained in six patients without a hiatal hernia during laparoscopic anterior esophageal myotomy for achalasia. Total protein extracts from tissue biopsies were analyzed for elastases MMP-2, -9, and -12 and collagenases MMP-1, -3, -7, -8, and -13 using a multiplex profiling kit (R&D Systems, Minneapolis, MN). Data are reported as mean +/- standard deviation. Statistical significance (p < 0.05) was determined using Tukey's test and analysis of variance.
  
  
  RESULTS
  In control patients without hiatal hernias, increased levels of MMP-2 (p < 0.02) were detected in the GHL compared with the GPL and PEL, respectively. Tissue levels of MMP-1, -12, and -13 were not detectable.
  
  
  CONCLUSIONS
  Gelatinase-A (MMP-2) is present in the GHL and plasma of control patients. The GHL may provide the primary GE junction supporting ligament to compare tissue from patients with type I (sliding) and type III (paraesophageal) hiatal hernias to examine the role of altered collagen metabolism in hiatal hernia formation.
authors.affiliation: Department of Surgery, Section of Minimally Invasive Surgery, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box #8109, St. Louis, MO 63110, USA. melmanl@wudosis.wustl.edu
authors.forename: Lora
authors.initials: L
authors.lastname: Melman
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Chisholm
authors.forename: John A
authors.initials: JA
authors.lastname: Curci
authors.forename: Batool
authors.initials: B
authors.lastname: Arif
authors.forename: Richard
authors.initials: R
authors.lastname: Pierce
authors.forename: Eric D
authors.initials: ED
authors.lastname: Jenkins
authors.forename: L Michael
authors.initials: LM
authors.lastname: Brunt
authors.forename: Christopher
authors.initials: C
authors.lastname: Eagon
authors.forename: Margaret
authors.initials: M
authors.lastname: Frisella
authors.forename: Kathleen
authors.initials: K
authors.lastname: Miller
authors.forename: Brent D
authors.initials: BD
authors.lastname: Matthews
mesh_terms: D004943:Esophagogastric Junction / Q000378:metabolism*; D006551:Hernia, Hiatal / Q000378:metabolism; D006801:Humans; D008022:Ligaments / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*
chemical_list: D020778:Matrix Metalloproteinase 2