Elevated Levels of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in the Acute Phase of Kawasaki Syndrome

Abstract

Background: Kawasaki syndrome (KS) is characterized by inflammation of coronary arteries and other medium-sized muscular arteries, leading to coronary aneurysms and thromboses. Matrix metalloproteinases (MMPs), a class of zinc-dependent, calcium-requiring enzymes capable of degrading extracellular matrices, are vital for extracellular remodeling. Elevated MMP-9 mRNA, protein and enzyme levels have previously been reported in adults with abdominal aortic aneurysm. Methods: Plasma or serum samples from KS patients (31) and febrile (9) and afebrile (17) controls were analyzed for MMP-9 enzyme and protein levels, as well as TIMP-1 protein levels, by gelatin zymography and ELISA. Results: Both MMP-9 enzyme and protein levels and TIMP-1 protein levels were significantly elevated in the acute phase of KS compared to their respective convalescent phase (mean MMP-9 enzyme: 114,754 pixels vs. 29,523 pixels; MMP-9 protein: 1,147 ng/mL vs. 193 ng/mL; TIMP-1 protein: 1,321 ng/mL vs. 651 ng/mL), as well as to febrile (MMP-9 enzyme: 114,754 pixels vs. 54,947 pixels; MMP-9 protein: 1,147 ng/mL vs. 428 ng/mL; TIMP-1 protein: 1,321 ng/mL vs. 600 ng/mL) and afebrile (MMP-9 enzyme: 114,754 pixels vs. 25,071 pixels; MMP-9 protein: 1,147 ng/mL vs. 110 ng/mL; TIMP-1 protein: 1,321 ng/mL vs. 552 ng/mL) controls. Conclusions: The markedly elevated levels of MMP-9 in the acute phase of KS may reflect vascular remodeling or an inflammatory response to a microbial agent. Furthermore, because MMP-9 and TIMP-1 in KS are significantly different from febrile controls, we are evaluating the usefulness of MMP-9 and TIMP-1 as a much needed diagnostic test for KS. [Supported by grants from RCMI program (G12RR/AI-03061), NCRR, NIH; American Heart Association (9960338Z); and Hawaii Community Foundation (990565)]