Differential regulation of MMP-2 in the gastrohepatic ligament of the gastroesophageal junction.
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.
Melman
Lora
L
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
Chisholm
Phillip R
PR
Curci
John A
JA
Arif
Batool
B
Pierce
Richard
R
Jenkins
Eric D
ED
Brunt
L Michael
LM
Eagon
Christopher
C
Frisella
Margaret
M
Miller
Kathleen
K
Matthews
Brent D
BD
D004943:Esophagogastric Junction / Q000378:metabolism*; D006551:Hernia, Hiatal / Q000378:metabolism; D006801:Humans; D008022:Ligaments / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*
D020778:Matrix Metalloproteinase 2