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Ramiprilate inhibits functional matrix metalloproteinase activity in Crohn's disease fistulas

Eva Efsen1, Torben Saermark, Alastair Hansen

  • 1Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Denmark. eefsen@yahoo.dk

Basic & Clinical Pharmacology & Toxicology
|May 4, 2011
PubMed

Insights

Matrix metalloproteinase (MMP) activity is elevated in Crohn's disease fistulas. The angiotensin-converting enzyme (ACE) inhibitor, ramiprilate, effectively reduced MMP-3 and MMP-9 activity, suggesting a potential therapeutic role.

Area of Science:

  • Gastroenterology
  • Biochemistry
  • Pharmacology

Background:

  • Matrix metalloproteinases (MMPs), specifically MMP-2, -3, and -9, are implicated in Crohn's disease (CD) fistulas.
  • The biological activity and therapeutic potential of these MMPs in CD fistulas remain unclear.

Purpose of the Study:

  • To investigate the proteolytic activity of MMPs in fistula tissues from CD patients.
  • To evaluate the efficacy of MMP inhibitors, including clinically available drugs, in suppressing this activity.

Main Methods:

  • Analysis of fistula specimens from 22 CD patients, 10 non-CD fistula patients, and 6 controls.
  • Measurement of total functional MMP activity using HPLC-based assays.
  • Specific activity assessment of MMP-2, -3, and -9 using Biotrak Activity Assay.
  • Testing MMP inhibitors: EDTA, GM6001, ramiprilate, and doxycycline.

Main Results:

  • MMP activity constituted approximately 50% of total protease activity in CD fistulas.
  • Significantly higher total MMP activity (3.5-fold) was observed in CD fistulas compared to non-CD fistulas and normal colon.
  • Elevated MMP-3 and MMP-9 specific activities were detected in CD fistulas.
  • Ramiprilate significantly reduced total MMP activity by 42% and MMP-3 activity by 72%, and completely inhibited MMP-9 activity.

Conclusions:

  • Increased functional MMP activity, particularly MMP-3 and MMP-9, is a characteristic of Crohn's disease fistulas.
  • Ramiprilate, an ACE inhibitor, demonstrates significant inhibitory effects on MMP activity in these fistulas.
  • Ramiprilate represents a potential therapeutic agent for managing Crohn's disease fistulas due to its MMP-inhibiting properties.

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