title: Disruption of Endothelial Cell Homeostasis Plays a Key Role in the Early Pathogenesis of Coronary Artery Abnormalities in Kawasaki Disease.
abstract: Disruption of endothelial cell homeostasis may be associated with the pathogenesis of coronary artery abnormalities (CAA) in Kawasaki disease (KD). We sought to clarify the poorly understood pathogenic role of endothelial cell survival and death in KD vasculitis. Human umbilical vein endothelial cells (HUVECs) stimulated with sera from KD patients, compared with sera from patients with bacterial infections, exhibited significant increases in cytotoxicity, high mobility group box protein 1 (HMGB-1), and caspase-3/7 and a decrease in phosphorylated Akt/Akt (pAkt/Akt) ratios. HUVECs stimulated with sera from KD patients treated with immunoglobulin (IG) showed significantly decreased cytotoxicity, HMGB-1, and caspase-3/7 levels and increased pAkt/Akt ratios, as compared with results for untreated HUVECs (P < 0.001, P = 0.008, P = 0.040, and P < 0.001, respectively). In HUVECs stimulated with sera from KD patients, the increased cytotoxicity levels and the suppression of increased pAkt/Akt ratios after subsequent IG treatment were closely related to the development of CAA (P = 0.002 and P = 0.035). Our data reveal that shifting the balance toward cell death rather than survival appears to perturb endothelial cell homeostasis and is closely related to the development of CAA. The cytoprotective effects of IG treatment appear to ameliorate endothelial cell homeostasis.
authors.affiliation: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ninomiya
authors.affiliation: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hazeki
authors.affiliation: Department of Pediatrics, Kagoshima City Hospital, Kagoshima Japan.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Department of Pediatrics, Kagoshima City Hospital, Kagoshima Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nomura
authors.affiliation: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kawano
mesh_terms: D001424:Bacterial Infections / Q000150:complications / Q000175:diagnosis / Q000382:microbiology; D015415:Biomarkers; D020169:Caspases / Q000378:metabolism; D002675:Child, Preschool; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D024243:HMGB1 Protein / Q000378:metabolism; D006706:Homeostasis; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases