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Hemorrhoids and matrix metalloproteinases: A multicenter study on the predictive role of biomarkers
Raffaele Serra1, Luca Gallelli2, Raffaele Grande3
1Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy; Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy.
Introduction:
An association between hemorrhoidal disease and matrix metalloproteinases (MMPs) has been described previously. MMPs regulate extracellular structural proteins and tissue remodeling. Neutrophil gelatinase-associated lipocalin (NGAL) is involved in the regulation of MMP activity. The aim of this work was to study the relationship between tissue immunoreactive levels of MMPs and NGAL and different stages of hemorrhoids.
Methods:
In a multicenter, open-label, prospective study, the population under investigation consisted of 2 groups: group I (with symptomatic hemorrhoids; Goligher grade I-IV) and group II (healthy volunteers).
Results:
We enrolled 97 patients with hemorrhoids: 21 with grade I hemorrhoids, 37 with grade II, 14 with grade III, and 25 with grade IV. Finally, 90 healthy volunteers (53 males and 37 females; age range, 19-70 years; median, 56) were enrolled in group II. Enzyme-linked immunosorbent assay and Western blot analysis revealed greater levels of immunoreactive MMPs and NGAL in all patients with hemorrhoids. We recorded significantly greater levels of MMP-1 and MMP-3 in grade I and II patients compared with control, and greater levels of MMP-3, MMP-7, MMP-8, and MMP-9 in grade III compared with grade II. MMP-9 and NGAL were particularly increased in patients with grade IV especially in case of thrombosed hemorrhoids.
Conclusion:
These results provide potentially important insights into the understanding of the natural history of hemorrhoids. MMPs and NGAL play a role in development of disease and may represent molecular markers for the complications such as hemorrhoidal thrombosis.
Insights
Matrix metalloproteinases (MMPs) and neutrophil gelatinase-associated lipocalin (NGAL) are elevated in hemorrhoidal disease. Levels increase with disease severity, suggesting roles in pathogenesis and potential markers for complications like thrombosis.
Area of Science:
- Gastroenterology
- Biochemistry
- Pathology
Background:
- Hemorrhoidal disease is associated with matrix metalloproteinases (MMPs), enzymes regulating tissue remodeling.
- Neutrophil gelatinase-associated lipocalin (NGAL) modulates MMP activity.
- Previous studies suggest a link between MMPs and hemorrhoids.
Purpose of the Study:
- To investigate the relationship between tissue levels of MMPs and NGAL and the severity of hemorrhoidal disease.
- To explore the potential role of these molecules in the natural history and complications of hemorrhoids.
Main Methods:
- A prospective, open-label study involving 97 patients with symptomatic hemorrhoids (Goligher grades I-IV) and 90 healthy volunteers.
- Tissue samples were analyzed for MMPs and NGAL using enzyme-linked immunosorbent assay and Western blot.
Main Results:
- Elevated levels of MMPs and NGAL were found in all hemorrhoid patients compared to controls.
- Specific MMPs (MMP-1, MMP-3, MMP-7, MMP-8, MMP-9) showed increased levels correlating with disease grade.
- MMP-9 and NGAL were significantly elevated in grade IV hemorrhoids, particularly with thrombosis.
Conclusions:
- MMPs and NGAL are implicated in the development of hemorrhoidal disease.
- These molecules may serve as valuable biomarkers for predicting disease progression and complications, such as hemorrhoidal thrombosis.
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