58 - CREATION AND EVALUATION OF MYOCARDIAL FIBROSIS USING A MOUSE MODEL OF KAWASAKI DISEASE VASCULITIS

(Background) Some articles have reported of myocardial fibrosis in adult patients with Kawasaki disease (KD) in autopsy cases without myocardial infarction; however, whether acute coronary arteritis leads to myocardial fibrosis remains unclear.  We used a mouse model of KD to create an myocardial fibrosis model and evaluated gradual changes in coronary arteritis and the function of fibrotic myocardium.

(Methods) Six -week-old male C57BL/6 mice were injected with FK565 (50 ug), a Nod1 ligand, on days 1 and 5, and isoproterenol (40 mg/kg/day) was administered continuously for 1 week starting from day 8.

Echocardiography was performed to evaluate cardiac function, and L-type Ca2+ current was measured using the patch clamp method. Cardiac  optical mapping was used to measure myocardial surface action potentials. Galectin-3 (Gal-3) and calprotectin, markers of inflammation and fibrosis, were measured using ELISA and compared with those of the control group.

(Results) EF decreased in the fibrosis model mice immediately after FK565 administration (55% vs. 67%), and  L-type Ca2+ current decreased. EF gradually improved, whereas pericoronary inflammatory cells decreased, and collagen fiber proliferation was observed 6 months after administration. Immunohistochemistry detected Gal-3-positive cells in fibrotic myocardium. Gal-3 and calprotectin peaked within 24 h after NOD1 ligand administration but did not increase thereafter.

Conclusion: Mouse model of myocardial fibrosis using FK565 may serve as a mouse model of distant-stage KD.