Abstract P083: Progression Of Vascular Dysfunction In A Mouse Model Of Kawasaki Disease

Abstract

Progression of vascular dysfunction in a mouse model of Kawasaki disease Alina Saiyid, Shubhnita Singh, Ariane Bruder-Nascimento, Thiago Bruder-Nascimento Kawasaki disease (KD) is an acute, self-limited vasculitis and the most common cause of acquired cardiovascular disease in young children. Although severe vascular inflammation is already well-established in KD, how the arteries functionally behave in acute and convalescent phases is poorly understood. Herein, we sought to investigate the vascular function using a mouse model of KD.KD was induced by the Candida albicans water-soluble fraction model (CAWS, 4mg/day for 5 days) in C57BL6/J male mice (5-6-week-old). Mice were divided into 3 groups: control (G0, PBS injections), 7-days post 1 CAWS injection (G7), and 28-days post 1 CAWS injection (G28). Heart and abdominal aorta (AA) were harvested for vasculitis characterization. Vascular function was studied in AA via wire myograph.G7 presented an increase in TNFα and IL1β gene expression in the heart and AA, but without clear vasculitis (analyzed by histology). However, G28 exhibited a severe immune cell infiltration in the aortic root, coronary arteries, and AA. In G7, AA displayed a drastic reduction in vascular response to norepinephrine [maximal response (Emax in mN): C: 5.4 ± 0.6 vs. G7: 2.0 ± 0.5*, *p<0.05], such attenuation was abolished by pre-treating the AA with L-NAME (nitric oxide synthase inhibitor). In G28, a mild change was observed in maximal response; however, increased sensitivity was found (pD2: C: 6.0 ± 0.4 vs. G28: 6.8 ± 0.3*, *p<0.05). After L-NAME pre-treatment, the difference persisted indicating a NO-dependent response. Furthermore, a severe endothelial dysfunction, characterized by impaired relaxation of acetylcholine, was observed in G28 [Emax (%): C: 85.7 ± 8.4 vs. G28: 54.8 ± 6.4*, *p<0.05].In conclusion, the acute phase of KD is associated with impaired vascular contractility via an excess of NO, which could justify some children presenting shock in clinic. In the convalescent phase (G28), the arteries are injured and likely with an irreversible phenotype. Thus, an adequate and punctual treatment for KD is highly requested.