Abstract 11827: Endothelial Microparticles Modulate Vasculitis During the Acute Phase of Kawasaki Disease
Introduction: Kawasaki Disease (KD) is an acute inflammatory disease that takes the form of systemic vasculitis. Endothelial microparticles (EMPs) are vesicles formed by cell membranes after endothelial activation, which contain microRNAs (miRs) recognized as an important transcellular delivery system in the exchange of biological signals. The purpose of this study was to elucidate whether EMPs are involved in vasculitis in acute KD.
Methods: We enrolled 50 KD patients (aged 4 months to 14 years), 50 controls (25 non-KD febrile and 25 healthy children). KD patients were divided into two subgroups: those with coronary artery lesions (CAL, Z-socre>2.5, n=4) and those without coronary artery lesions (NCAL, Z-score≦2.5, n=46). Blood samples were collected three times; first, at the time of diagnosis before the initiation of IVIG treatment; second, immediately after the first IVIG infusion; finally, at 2-4 weeks after the onset of the disease. EMPs were measured using flow cytometry and miR expression profiling was performed using microarrays (Affymetrix® GeneChip® miRNA 4.0). We also performed miRCURY LNA™ microRNA in situ hybridization using 2 miRs in CAL patients and analyzed THP-1 monocyte stimulation using 2 miRs.
Results: The percentage of EMPs was 1.27±0.16% in all of the small vesicles in KD patients prior to treatment, which was significantly higher than in controls (0.09±0.03%: P<0.0001). Furthermore the percentage of EMPs in patients with CAL rapidly increased after the initial treatment, and was significantly higher than those without CAL (p<0.001). We identified two miRs (hsa-miR-145-5p and hsa-miR-320a) out of 2578 miRs (0.08%) specific to the patients with CAL and these two miRs are predicted to affect the monocyte system using in silico analysis. We also detected these two miRs in CAL patients’ endothelial cells, using in situ hybridization, and showed these two miRs suppressed gene expression of the two inflammatory cytokines (IL-6 and TNF-α).
Conclusions: EMPs could serve as a sensitive marker of the severity of endothelial dysfunction and vasculitis in acute KD. Moreover, hsa-miR-145-5p and hsa-miR-320a may contribute to regulation of gene expression of cytokines and pathogenesis of KD.
Author Disclosures: H. Nakaoka: None. K. Hirono: None. M. Okabe: None. N. Miyao: None. K. Saito: None. K. Ibuki: None. S. Ozawa: None. K. Takahashi: None. F. Ichida: None.
- © 2016 by American Heart Association, Inc.