Background: Kawasaki disease (KD) is the most common cause of acute systemic vasculitis and acquired cardiac disease among US children. KD causes coronary artery aneurysms in up to 25% of untreated patients, and less frequently aneurysms in other systemic arteries including the abdominal aorta. Lactobacillus casei cell wall extract (LCWE)-induced KD mouse model mimics histopathologically the coronary artery lesions seen in KD patients.
Objective: To evaluate the development of abdominal aorta dilatation and aneurysm in KD mouse model and investigate the role of IL-1 signaling.
Methods and Results: We investigated the incidence and progression of abdominal aorta aneurysm (AAA) and dilatation in the KD model at 1, 2, 5 weeks. Over 80% of the mice developed significant dilation of abdominal aorta at 2 wks with progressively greater dilatation at 5 wks, with greater severity in males. KD mice showed fusiform and saccular AAA, which were always below the renal artery. Immunohistochemistry showed significant intimal proliferation, massive myofibroblastic proliferation that breaks the elastin layer, infiltration of large numbers of neutrophils and macrophages into the media and adventitia. IL-1R- or IL-1beta-deficient mice were completely protected from the KD associated abdominal aorta dilatation and AAA. IL-1R antagonist (Anakinra) significantly prevented the abdominal aorta dilatation and AAA (in addition to blocking coronary arteritis) in the KD mice.
Conclusions: We report a new model of AAA and aortic dilatation in the LCWE-induced KD mouse model. These studies suggest that in children with KD the incidence of abdominal aortic dilatation and AAA maybe higher than currently appreciated, thus requiring prospective studies to determine the frequency of these vascular complications. Our findings also demonstrate that IL-1 plays an important role in development of LCWE-induced abdominal aortic lesions and blockade of IL-1 signaling may be a promising therapeutic target not only for KD vasculitis and coronary arteritis, but also for abdominal aorta dilatation and AAA associated with the disease.