Effect of angiotensin-converting enzyme inhibitor on matrix metalloproteinase-9 activity in patients with Kawasaki disease

Clin Chim Acta. 2010 Feb;411(3-4):267-9. doi: 10.1016/j.cca.2009.11.020. Epub 2009 Nov 27.

Abstract

Background: Matrix metalloproteinase (MMP)-9 is thought to be involved in coronary artery aneurysms (CAAs) in patients with Kawasaki disease (KD); however, MMP-9 inhibitors are not used clinically. This study investigated whether the angiotensin-converting enzyme (ACE) inhibitor captopril could inhibit serum MMP-9 activity using serum from KD patients in an in vitro experiment.

Methods: In 7 KD patients, serum MMP-9 activity was measured using the MMP-9 assay kit 3 times: before and after intravenous immunoglobulin (IVIG) treatment, and during the convalescent phase. The effect of captopril on MMP-9 activity was also assessed using serum obtained before IVIG treatment.

Results: Serum MMP-9 activity was significantly higher during the pre-treatment phase than during the post-treatment and convalescent phases. MMP-9 activity during the pre-treatment phase was dose-dependently inhibited by captopril, and the IC(50) for MMP-9 was 500nM. The potency of captopril for MMP-9 inhibition was comparable to that for ACE inhibition.

Conclusion: ACE inhibitor may be effective for preventing CAA formation in KD patients, especially IVIG non-responders.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Captopril / pharmacology*
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infant
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Matrix Metalloproteinase Inhibitors
  • Mucocutaneous Lymph Node Syndrome / blood
  • Mucocutaneous Lymph Node Syndrome / enzymology*
  • Peptidyl-Dipeptidase A / metabolism*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • Captopril
  • Peptidyl-Dipeptidase A
  • Matrix Metalloproteinase 9