MEF2C mitigates coronary artery lesions in Kawasaki disease by enhancing endothelial barrier function through KLF2 regulation

Coronary artery lesions constitute a significant complication of Kawasaki disease (KD) and represents one of the primary etiologies of acquired cardiovascular disease in pediatric populations. In the present study, we observed a downregulation of MEF2C expression in the whole blood of KD patients and in human coronary artery endothelial cells (HCAECs) during the pathophysiological progression of KD. Furthermore, transcriptomic data analysis, in conjunction with observations from HCAECs stimulated with KD serum, indicates that the downregulation of MEF2C in KD is correlated with increased inflammatory levels and the activation of inflammatory pathways. Overexpression of MEF2C has the potential to mitigate inflammation and apoptosis in HCAECs, whereas MEF2C knockdown exhibits contrary effects. Furthermore, MEF2C overexpression may alleviate inflammation and apoptosis in the coronary endothelium, attenuate abdominal aortic dilation, and prevent the decline of cardiac function in a CAWS-induced KD murine model. Mechanistically, MEF2C overexpression safeguards against KD-induced endothelial barrier disruption and the downregulation of endothelial junction proteins in coronary injury associated with KD. Additionally, through RNA sequencing, we identified that KLF2 might be involved in the MEF2C-mediated protection against coronary endothelial injury. Employing a gene interference methodology, we substantiated that MEF2C mitigates coronary artery injury in KD via KLF2-regulated endothelial barrier protection in HCAECs. These findings suggest that MEF2C could serve as a potential therapeutic target for the prevention and treatment of coronary lesions in KD.