Cell adhesion molecule expression in coronary artery aneurysms in acute Kawasaki disease.
BACKGROUND
The pathogenesis of coronary artery aneurysm (CAA) formation in acute Kawasaki disease (KD) remains unclear. Cell adhesion molecules mediate cell-cell and cell-matrix interactions and regulate leukocyte migration, angiogenesis and tissue remodeling. We hypothesized that cell adhesion molecules are expressed in acute KD CAA.


METHODS
: P-selectin, E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and integrin beta1 were immunolocalized in coronary arteries from 6 acute KD patients and 7 controls.


RESULTS
In endothelial cells of adventitial neovasculature in KD CAA, P-selectin and integrin beta1 were expressed in all of 6 patients, and E-selectin and/or VCAM-1 were expressed in 4 of 6. Endothelial cells in controls and in nonaneurysmal KD coronary arteries expressed P-selectin and integrin beta1, but not E-selectin or VCAM-1. Integrin beta1 was expressed on infiltrating leukocytes in 5 of 6 KD CAA and on fibroblasts in 6 of 6; these findings were absent in controls and in nonaneurysmal KD coronary arteries.


CONCLUSIONS
The lack of widespread expression of E-selectin or VCAM-1 on endothelial cells of acute KD coronary arteries was surprising and suggests that inflammatory cell infiltration into KD coronaries is not simply the result of widespread up-regulation of cell adhesion molecules on endothelial cells by circulating cytokines. Rather, inflammatory cells may be directed to specific areas of the coronary arteries targeted by a pathogen causing KD. Our results suggest that E-selectin and VCAM-1 expression on neovasculature may contribute to neoangiogenesis and prolonged CAA inflammation and that integrin beta1 might be involved in fibroblastic remodeling of acute KD CAA.
Miura
Masaru
M
Department of Pediatrics, Northwestern University, The Feinberg School of Medicine and The Children's Memorial Hospital, Chicago, IL, USA.
Garcia
Francesca L
FL
Crawford
Susan E
SE
Rowley
Anne H
AH
D000293:Adolescent; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002648:Child; D003323:Coronary Aneurysm / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D013194:Staining and Labeling
D015815:Cell Adhesion Molecules