Targeting STAT3 pathway attenuates macrophages inflammation and cardiovascular injury in a model of Kawasaki disease.

Signal transducer and activator of transcription (STAT) 3 contributes to the development of cardiovascular diseases by modulating macrophages inflammation. However, the underlying implication of STAT3 pathway in Kawasaki disease (KD) has not been fully elucidated. Our reserach endeavors to investigate the potential role of STAT3 in macrophages inflammatory response and cardiovascular injury in the Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis model. In vitro experiments, we found that STAT3 was highly phosphorylated in LCWE-treated RAW264.7 macrophages and STAT3 blockade by AG490 significantly inhibited LCWE-mediated inflammatory response in RAW264.7 macrophages and mouse primary peritoneal macrophages. Furthermore, inhibition of macrophages STAT3 signaling attenuated mouse coronary endothelial cells damage induced by RAW264.7 cells-conditioned medium. In vivo experiments, our results showed that the protein level of phospho (p)-STAT3 was upregulated in the heart tissue of LCWE-injected mice and pharmacological inhibition of STAT3 with AG490 mitigated cardiac inflammation and vascular injury in the LCWE-induced KD mouse model. Collectively, our study reveals that targeting STAT3 pathway alleviates KD-associated macrophages inflammation and cardiovascular lesions and STAT3 may be a promising therapeutic target for KD.