Circulating Matrix Metalloproteinases and Their Inhibitors in Patients with Kawasaki Disease

Abstract

Background — Accelerated matrix breakdown caused by the increased activity of matrix metalloproteinases (MMPs) and/or the quantitative imbalance between MMP and tissue inhibitor of MMP (TIMP) have been implicated in several pathological conditions. MMP and TIMP may also be involved in the destruction of the coronary arterial wall and the resultant coronary arterial lesions in Kawasaki disease. Methods and Results — Plasma levels of MMPs, neutrophil elastase, and TIMPs were measured by enzyme-linked immunoassay in 57 patients with Kawasaki disease and no coronary arterial lesions (group 1) and in 8 patients with Kawasaki disease and coronary arterial lesions (group 2). Blood samples were obtained before and after intravenous gamma globulin therapy and in the convalescent stage. Levels of MMPs, neutrophil elastase, and TIMPs were significantly higher in Kawasaki disease patients before gamma globulin therapy than in 18 age-matched afebrile control subjects and 17 age-matched febrile disease control subjects ( P <0.01). More importantly, the pre-gamma globulin MMP9 level and MMP9/TIMP2 ratio and post-gamma globulin MMP3 level and MMP3/TIMP1 ratio were significantly higher in group 2 than in group 1 patients ( P <0.05). Although MMP levels in febrile disease controls were significantly higher than those of afebrile controls, the MMP/TIMP ratios of febrile disease controls and afebrile controls were comparable. Conclusions — These data suggest that patients with Kawasaki disease and high levels of MMP and/or MMP/TIMP are susceptible to coronary arterial lesions. Studies of the effects of MMP inhibitors on coronary outcome may provide evidence that MMP is a viable therapeutic target for the prevention of coronary arterial lesions due to Kawasaki disease.