[P64-6] 川崎病マウスモデルにおける電気生理学的リモデリング
Keywords:Kawasaki Disease, Model mouse, remodeling
Background:40 to 80% of children with Kawasaki Disease (KD) frequently show ECG abnormalities suggestive of myocarditis. Objective: To investigate if the Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis mouse model is associated with cardiac nerve remodeling and electrophysiological changes similar to abnormalities clinically reported in KD children. Methods and Results: KD mice and IL-1R antagonist (Anakinra; daily i.p. for 1 week) treated KD mice (KD+IL-1Ra) were examined and ECG studies were performed weekly for three weeks. We observed elevated heart rate in KD mice compared with controls and this tachycardia was prevented with IL-1Ra. the R wave amplitude at 1 week of KD mice decreased compared with control, and significant differences in prolonged ventricular repolarization (long QT) at 2 weeks were detected; both process were prevented by IL-1Ra. Serum NGF levels and it’s gene expression in myocardium were significantly elevated in KD mice and reduced in KD+IL-1Ra mice. Finally, neural remodeling, assessed by GAP43 and TH immunostaining in heart tissue sections, was significantly increased in KD mice and this process was also dependent of IL-1 signaling as neural remodeling was significantly decreased in LCWE-injected IL-1R KO mice. Conclusions:KD vasculitis mouse model mimics the electrophysiological abnormalities reported in KD children. Treatment with Anakinra prevents ECG abnormalities and elevated NGF serum concentrations. We also confirmed that KD associated cardiac neural remodeling occurs in this mouse model and is IL-1 dependent.