Matrix metalloproteinase 9 activity leads to elastin breakdown in an animal model of Kawasaki disease

Arthritis Rheum. 2008 Mar;58(3):854-63. doi: 10.1002/art.23225.


Objective: Kawasaki disease (KD) is a multisystem vasculitis leading to damage in the coronary circulation and aneurysm formation. Because cardiac tissue from affected children is not available, investigation of the mechanisms responsible for coronary artery damage in KD requires use of a disease model. The present study was undertaken to examine, in an experimental model, the role of matrix metalloproteinase 9 (MMP-9) on coronary artery inflammation and vascular damage.

Methods: C57BL/6 mice were injected with Lactobacillus casei cell wall extract to induce coronary arteritis. Hearts were isolated and assayed for MMP-9 protein expression and enzymatic activity by immunoblotting or confocal microscopy and zymography, respectively. MMP-9-deficient mice were used to examine the necessity of MMP-9 for disease development.

Results: Localized inflammation at the coronary artery led to elastin breakdown and aneurysm formation. This occurred in the absence of smooth muscle cell apoptosis. Following disease induction, there was an increase in the amount and enzymatic activity of MMP-9, an elastolytic protease. MMP-9 was up-regulated by tumor necrosis factor alpha (TNFalpha) and produced primarily by vascular smooth muscle cells. In MMP-9-deficient animals, vascular inflammation continued to develop, but the incidence of elastin breakdown was significantly reduced. Elastin breakdown in the coronary artery was virtually eliminated by ablation of MMP-9.

Conclusion: These findings show that TNFalpha up-regulates expression of MMP-9, an important proteinase responsible for extracellular matrix breakdown, leading to coronary artery damage in this model of KD. These results have important implications regarding treatments for improving coronary outcome in affected children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bacterial Proteins
  • Coronary Artery Disease / chemically induced
  • Coronary Artery Disease / enzymology
  • Coronary Artery Disease / pathology
  • Coronary Vessels / enzymology
  • Coronary Vessels / pathology
  • Disease Models, Animal
  • Elasticity
  • Elastin / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Lacticaseibacillus casei
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mucocutaneous Lymph Node Syndrome / enzymology*
  • Mucocutaneous Lymph Node Syndrome / pathology
  • Muscle, Smooth, Vascular / enzymology
  • Muscle, Smooth, Vascular / pathology
  • Tumor Necrosis Factor-alpha / metabolism


  • Bacterial Proteins
  • Tumor Necrosis Factor-alpha
  • Elastin
  • Matrix Metalloproteinase 9