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A local imbalance between MMP and TIMP may have an implication on the severity and course of appendicitis
Anna Solberg1, Lena Holmdahl, Peter Falk
1Department of Surgery, Colorectal Unit, Sahlgrenska University Hospital/Ostra, Gothenburg University, Gothenburg, Sweden. anna.solberg@surgery.gu.se
Background:
Matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) have been demonstrated to be involved in inflammatory conditions in the intestine. The purpose of this study was to investigate whether the alterations of the MMP/TIMP balance might reflect the course of the inflammatory process in acute appendicitis and if the expression and localisation of MMPs and TIMP is variable in the various clinical manifestations of appendicitis.
Materials And Methods:
The study comprises 40 patients (26 men and 14 women) having emergency appendectomy and a control group constituting of 10 patients (5 men and 5 women) having a hemicolectomy for other reasons. MMP and TIMP expressions were assessed and compared in tissue specimens from phlegmonous (n = 15), gangrenous (n = 7), perforated appendicitis (n = 11) and controls with noninflamed appendices (n = 10) by means of enzyme-linked immunosorbent assay technique. Localisation of the enzymes was performed by immunohistochemistry.
Results:
MMP-1 was significantly higher in gangrenous and perforated appendicitis compared with phlegmonous appendicitis and controls (p < 0.05) while MMP-2 was significantly lower in gangrenous appendicitis compared with phlegmonous appendicitis and controls. MMP-2 was also lower in perforated appendicitis when compared with controls (p < 0.01). Elevated expression of MMP-9 was demonstrated in all groups of appendicitis compared with the controls (p < 0.001).
Conclusions:
MMP-9 is the most abundantly expressed MMP of those investigated in inflamed appendix. We postulate that a local imbalance between MMP-9 and TIMP-1 may trigger a perforation. These results suggest that MMPs might be useful as biomarkers of appendices prone to perforation.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) show altered levels in appendicitis. Elevated MMP-9 in inflamed appendices suggests it may be a biomarker for perforation risk.
Area of Science:
- Gastroenterology
- Surgical Pathology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are implicated in intestinal inflammation.
- Their role in acute appendicitis and varying clinical presentations requires further investigation.
Purpose of the Study:
- To investigate MMP/TIMP balance alterations in acute appendicitis.
- To determine if MMP and TIMP expression and localization vary with appendicitis severity.
Main Methods:
- Tissue specimens from 40 appendectomy patients (phlegmonous, gangrenous, perforated) and 10 controls were analyzed.
- Enzyme-linked immunosorbent assay (ELISA) assessed MMP and TIMP expression.
- Immunohistochemistry localized enzyme expression.
Main Results:
- MMP-1 was elevated in gangrenous and perforated appendicitis versus controls.
- MMP-2 was lower in gangrenous and perforated appendicitis compared to controls.
- MMP-9 showed significantly elevated expression in all appendicitis groups versus controls.
Conclusions:
- MMP-9 is highly expressed in inflamed appendices.
- An imbalance between MMP-9 and TIMP-1 may contribute to perforation.
- MMPs show potential as biomarkers for predicting appendiceal perforation.
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