Integrins α4 and αM, collagen1A1, and matrix metalloproteinase 7 are upregulated in acute Kawasaki disease vasculopathy.
BACKGROUND
Kawasaki disease (KD) can result in fatal coronary artery (CA) aneurysms, especially if left untreated. Our recent studies of its vascular pathology revealed subacute/chronic vasculitis that begins early in the illness with the proliferation of smooth muscle cell-derived myofibroblasts in a complex extracellular matrix (ECM). We hypothesized that a dysregulation of specific ECM and adhesion molecules occurs in KD CAs.


METHODS
Gene expression profiling for ECM and adhesion molecules was performed on six acute KD and eight control CAs using a targeted real-time PCR array approach.


RESULTS
Integrins α4 and αM (ITGA4, ITGAM), collagen type I, α1 (COL1A1), and matrix metalloproteinase 7 (MMP7) were significantly upregulated in KD CAs as compared with controls. Immunohistochemistry with anti-ITGAM antibodies revealed expression on inflammatory cells within the CA wall in patients with KD but not in controls.


CONCLUSIONS
Integrins ITGA4 and ITGAM are upregulated in KD vasculopathy, probably promoting inflammatory recruitment that stimulates smooth muscle cell transition to myofibroblasts and their proliferation. MMP7 probably enhances myofibroblast proliferation and luminal lesion expansion, and overexpression of COL1A1 may lead to CA stenosis. Identification of the molecular pathogenesis of KD vasculopathy may lead to the development of circulating biomarkers and to directed therapeutic interventions.
Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
Rebecca
R
Reindel
Susan C
SC
Baker
Kwang-Youn
KY
Kim
Carol A
CA
Rowley
Stanford T
ST
Shulman
Jan M
JM
Orenstein
Elizabeth J
EJ
Perlman
Mark W
MW
Lingen
Anne H
AH
Rowley
D039481:CD11b Antigen / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D003331:Coronary Vessels / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry; D039441:Integrin alpha4 / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D009080:Mucocutaneous Lymph Node Syndrome / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction
D039481:CD11b Antigen; D015815:Cell Adhesion Molecules; D024042:Collagen Type I; D039441:Integrin alpha4; D020783:Matrix Metalloproteinase 7