The Imbalance between Matrix Metalloproteinase-9, -2 and Tissue Inhibitor of Metalloproteinases-1 in Acute Phase Kawasaki Disease

Background: Matrix metalloproteinases (MMPs) have been considered to play a pivotal role in extracellular matrix breakdown. The activity of MMPs is closely regulated by tissue inhibitors of metalloproteinases (TIMPs) under the pathophysiological conditions. In recent studies, the quantitative imbalance between certain MMPs and TIMPs may play an important role in the vascular remodeling process. Objective and Methods: To investigate the role of MMPs and TIMPs in vasculitis of patients with acute phase Kawasaki disease (KD), we sequentially measured the serum levels of MMP-1, 2, 3, TIMP-1, -2, and the plasma levels of MMP-9 using rapid one-step sandwich enzyme immunoassay before and after IVGG treatment. Nineteen patients (13 boys and 6 girls; 17.4±10.1 months of the mean age) with acute KD were studied. Results: The serum levels of MMP-1 and -3 before treatment were slightly elevated compared to normal range of adults reported in previous literatures and returned to normal range after 1 month. MMP-2 levels were slightly elevated before treatment and remained that level through 1 month later (p<0.01). The plasma levels of MMP-9 and serum levels of TIMP-1 were significantly elevated before treatment and returned to normal range 1 month later (p<0.05, p<0.01). Consequently, the ratio of MMP-2/TIMP-1 decreased, and MMP-9/TIMP-1 increased gradually after the IVGG treatment (p<0.01, p<0.01). Conclusion: We speculate that the imbalance between MMP-9, MMP-2 and TIMP-1 may play an important role in acute phase KD.