Kawasaki disease (KD), the leading cause of acquired
cardiac disease among children, is often associated with
myocarditis that may lead to long-term myocardial dysfunction and
fibrosis. Although those myocardial changes develop during the acute phase, they may persist for decades and closely correlate with long-term myocardial sequelae. Using the Lactobacillus casei cell wall extract-induced (LCWE-induced) KD
vasculitis murine model, we investigated long-term cardiovascular sequelae, such as myocardial dysfunction,
fibrosis, and coronary microvascular lesions following
adrenergic stimuli after established KD
vasculitis. We found that
adrenergic stimulation with
isoproterenol following LCWE-induced KD
vasculitis in mice was associated with increased risk of
cardiac hypertrophy and myocardial
fibrosis, diminished ejection fraction, and increased serum levels of
brain natriuretic peptide. Myocardial
fibrosis resulting from pharmacologic-induced exercise after KD development was
IL-1 signaling dependent and was associated with a significant reduction in myocardial capillary CD31 expression, indicative of a rarefied myocardial capillary bed. These observations suggest that
adrenergic stimulation after KD
vasculitis may lead to
cardiac hypertrophy and bridging
fibrosis in the myocardium in the LCWE-induced KD
vasculitis mouse model and that this process involves
IL-1 signaling and diminished microvascular circulation in the myocardium.