Abstract

Introduction: Kawasaki disease (KD) is an acute systemic vasculitis, which might promote atherosclerosis in adulthood. The purpose of this study is to verify long-term effect of HMG-CoA inhibitor (statin) for the vasculitis. Hypothesis: Statins suppressed inflammatory cell infiltration and plaque arteriosclerosis in KD, and might have a preventive effect on the onset of cardiovascular events in the chronic phase. Methods: Candida albicans water-soluble fraction (CAWS) was injected intraperitoneally in 5-week-old male apoE -/- mice to create KD-like vasculitis. All mice were fed a high-fat diet 2 weeks after the first injection. Divided into 3 groups, PBS (P), CAWS (C), and CAWS with statin (CS) (orally administered atorvastatin 10mg/kg/day), and sacrificed 6 or 10 weeks after injection and obtained the aorta with the heart (from root to iliac bifurcation). The lipid plaque lesion on the aorta was stained with Oil Red O and the inflammatory cells in aortic root sections were stained with hematoxylin and eosin. These area ratios were quantified and compared. Results: Both atherosclerosis and inflammatory cell infiltration were significantly promoted by CAWS (p<0.01). Statin significantly suppressed plaque area after 10 weeks (C 33±1.5%, CS 18±1.7%) and inflammatory cell infiltration after 6, 10 weeks (C 16±0.6%, CS 7.8±0.9% after 6 weeks, and C 20±2.1%, CS 10±1.0 after 10 weeks, respectively). We examined the statistical correlation between the plaque lesion and the inflammatory cell area, so it revealed the trend between the two groups (r=0.97, P<0.001). Conclusions: CAWS vasculitis, KD-like vasculitis, promoted the development of atherosclerosis in apoE -/- mice. It was newly revealed that long-term oral administration of statin significantly suppressed not only atherosclerosis but also inflammatory cell infiltration. Statin treatment might be expected for secondary prevention of the onset of cardiovascular events in the chronic phase of KD.

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