A novel mouse model of coronary stenosis mimicking Kawasaki disease induced by Lactobacillus casei cell wall extract

Abstract

Kawasaki disease (KD), a febrile systemic vasculitis in infants associated with coronary aneurysm, is a major cause of cardiac sequelae such as myocardial infarction (MI) and sudden death. These events are caused by coronary stenosis due to intimal proliferation or thrombotic formation; however, histological evaluation is limited to autopsy cases of human KD. We therefore investigated the histological features of coronary artery (CA) stenosis in mice induced by Lactobacillus casei cell wall extract (LCWE). LCWE-induced coronary inflammation gradually progressed in a time-dependent manner and expanded to all layers of the vessel wall over 28 days. In addition, frequent elastin degradation was observed and abundant α-smooth muscle actin (SMA)-positive vascular smooth muscle cells (VSMCs) infiltrated into the intima. Furthermore, most VSMCs were positive for proliferating cell nuclear antigen (PCNA) following staining, suggesting that VSMCs likely exhibited a proliferative phenotype. In conclusion, we show a novel mouse model of coronary stenosis induced by LCWE that is characterized by coronary stenosis with severe coronary vasculitis and elastin degradation. In addition, VSMC proliferation plays an important role in the formation of coronary stenosis. This model is an appropriate model of KD coronary stenosis.