Abstract 12008: Increased Circulating Endothelial Microparticles in the Acute Phase of Kawasaki Disease

Abstract

Introduction: Kawasaki disease(KD) is a typically acute inflammatory syndrome that takes the form of systemic vasculitis. The acute inflammation and subsequent reparative process may lead to lasting changes in arterial structure even in the convalescence of KD including increased endothelial dysfunction. Endothelial microparticles(EMPs) are vesicles formed by the cell membrane after endothelial activation. EMPs typically contain microRNAs(miRs). MiRs can affect mRNA degradation and translation. EMPs may transfer information from the parent cell to various target cells by direct cell-to-cell contact or alternatively through secretion of soluble mediators and effectors. Methods: We enrolled 35 patients (aged 3 months to 14 years, 21 male, 14 female), 35 controls. KD patients were divided into two subgroups; coronary artery lesion (CAL, Zsocre>2.5, n=5) and no coronary lesion (NCAL, Zscore≦2.5, n=30). Blood samples were collected at the time of diagnosis before the initiation of IVIG treatment, then immediately after the first IVIG infusion and at 2-4 weeks after disease onset. EMPs were measured by using flow cytometry, and we performed miR expression profiling by using microarrays(Affymetrix® GeneChip® miRNA 4.0). Results: The percentage counts of EMPs were 2.90±1.26% in KD children before initial treatment, which were significantly higher (P<0.005) than those of controls (0.09±0.08%). The highest percentage count of EMPs (5.47%) was observed in the patient with CAL before initial treatment. In the patients with acute phase of KD with CAL, miR-320a (Fold change 22.66), miR-320b (Fold change 17.52) and miR-320c (Fold change 11.78) which were extracted from EMPs were up-regulated, while miR-550a (Fold change -4.81) and miR-3613-3p (Fold change -5.51) were down-regulated in comparison with those in convalescent phase. These 5 miRs were normalized after treatment. Conclusions: These results suggested that EMPs could serve as a sensitive marker of the severity of endothelial dysfunction and vasculitis in patients with KD. Moreover, miR-320 may have a pivotal role of vasculitis and the development of CAL during acute phase of KD.