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Disruption of Endothelial Cell Homeostasis Plays a Key Role in the Early Pathogenesis of Coronary Artery Abnormalities in Kawasaki Disease.
- Source :
-
Scientific reports [Sci Rep] 2017 Mar 03; Vol. 7, pp. 43719. Date of Electronic Publication: 2017 Mar 03. - Publication Year :
- 2017
-
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.
- Subjects :
- Bacterial Infections complications
Bacterial Infections diagnosis
Bacterial Infections microbiology
Biomarkers
Caspases metabolism
Child, Preschool
Coronary Vessels pathology
Female
Fluorescent Antibody Technique
HMGB1 Protein metabolism
Homeostasis
Human Umbilical Vein Endothelial Cells metabolism
Humans
Infant
Male
Mucocutaneous Lymph Node Syndrome diagnosis
Phosphorylation
Proto-Oncogene Proteins c-akt metabolism
Coronary Vessels metabolism
Endothelial Cells metabolism
Mucocutaneous Lymph Node Syndrome etiology
Mucocutaneous Lymph Node Syndrome metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28255175
- Full Text :
- https://doi.org/10.1038/srep43719