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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:576.)
© 2003 American Heart Association, Inc.

Vascular Biology

Systemic Arterial Expression of Matrix Metalloproteinases 2 and 9 in Acute Kawasaki Disease

Patrick J. Gavin; Susan E. Crawford; Stanford T. Shulman; Francesca L. Garcia; Anne H. Rowley

From the Division of Infectious Disease (P.J.G., S.T.S., A.H.R.), Children’s Memorial Hospital, and the Departments of Pediatrics (P.J.G., S.T.S., F.L.G., A.H.R.), Microbiology and Immunology (A.H.R.), and Pathology (S.E.C.), Northwestern University, Feinberg School of Medicine, Chicago, Ill.

Reprint requests to Anne H. Rowley, MD, Ward 12-204, Pediatrics W-140, Northwestern University, Feinberg School of Medicine, 303 E Chicago Ave, Chicago, IL 60611. E-mail a-rowley{at}northwestern.edu

Objective— Coronary artery aneurysms are the major complication of Kawasaki disease (KD). Matrix metalloproteinases (MMPs) regulate remodeling and degradation of the extracellular matrix. We hypothesized that MMP-9 expression is increased in acute KD aneurysms when compared with KD nonaneurysmal arteries and arteries from control children.

Methods and Results— MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 were immunolocalized in coronary arteries from children with fatal acute KD and controls. In KD coronary aneurysms, MMP-2 expression was prominent in the thickened neointima and in endothelial cells of new capillaries in areas of angiogenesis. MMP-9 was absent in control coronary arteries but was expressed in coronary artery aneurysms, nonaneurysmal coronary and noncoronary arteries, and cardiac nerves in acute KD, without an increase in TIMP-1 expression.

Conclusions— MMP-2 likely participates in remodeling of the arterial wall in acute KD, particularly in the processes of neointimal proliferation and angiogenesis. MMP-9 may play a role in the development of coronary aneurysms, but its expression is not confined to aneurysmal arteries. Systemic arterial expression of MMP-9 in acute KD, even in the absence of inflammatory changes in the vessel, suggests induction by a circulating factor, or possibly by an infectious agent with tropism for arterial tissue.

Key Words: Kawasaki disease • matrix metalloproteinases • coronary artery • aneurysm

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