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.