Systemic arterial expression of matrix metalloproteinases 2 and 9 in acute Kawasaki disease.
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.


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.
Gavin
Patrick J
PJ
Division of Infectious Disease, Children's Memorial Hospital, Chicago, Ill, USA.
Crawford
Susan E
SE
Shulman
Stanford T
ST
Garcia
Francesca L
FL
Rowley
Anne H
AH
D000208:Acute Disease; D002648:Child; D003323:Coronary Aneurysm / Q000201:enzymology / Q000209:etiology; D003331:Coronary Vessels / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D004549:Elastin / Q000032:analysis; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D017539:Tunica Intima / Q000201:enzymology
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D004549:Elastin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9