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Marimastat inhibits elastin degradation and matrix metalloproteinase 2 activity in a model of aneurysm disease
- Source :
- The British journal of surgery. 86(8)
- Publication Year :
- 1999
-
Abstract
- Background Abdominal aortic aneurysms are characterized by degradation of the extracellular matrix, with a reduction in the elastin concentration of the arterial media. These changes have been linked to increased levels of endogenous metalloproteinases (MMPs) within the aorta, particularly MMP-2 and MMP-9. This provides a potential therapeutic target for pharmacological agents aimed at reducing the growth rate of small aneurysms. In this study, the ability of marimastat (an MMP inhibitor) to reduce matrix degradation was assessed in a previously described model of aneurysm disease. Methods Porcine aortic segments (n = 12) were preincubated in exogenous pancreatic elastase for 24 h before culture in standard conditions for 13 days with marimastat 10−5, 10−6 and 10−7 mol/l. Control segments were cultured both without marimastat and without elastase. At the termination of culture, MMPs were extracted from the tissue and quantified by substrate gel enzymography. The volume fractions of elastin and collagen were determined by stereological analysis of sections stained with Miller's elastin and van Gieson's stain. Results Stereological analysis demonstrated preservation of elastin in aorta treated with marimastat at 10–6 and 10–5 mol/l; this was significant at the latter concentration (P = 0·007). This was accompanied by a significant reduction in active MMP-2 activity in the samples treated with marimastat 10–5 mol/l (P < 0·01). Conclusion Marimastat significantly inhibited elastin degradation and active MMP-2 production within aortic organ cultures.
- Subjects :
- Pathology
medicine.medical_specialty
Swine
Matrix metalloproteinase
Pharmacology
Hydroxamic Acids
Extracellular matrix
medicine.artery
Van Gieson's stain
medicine
Animals
Enzyme Inhibitors
Pancreatic elastase
Cells, Cultured
Aorta
biology
business.industry
Elastase
Metalloendopeptidases
Elastin
Extracellular Matrix
Gelatinases
biology.protein
Matrix Metalloproteinase 2
Surgery
business
Marimastat
medicine.drug
Aortic Aneurysm, Abdominal
Subjects
Details
- ISSN :
- 00071323
- Volume :
- 86
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- The British journal of surgery
- Accession number :
- edsair.doi.dedup.....cfdcb8122cadf99714967fe96052aabf