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

Area of Science:

• Cardiovascular Research
• Pediatric Cardiology
• Molecular Biology

Background:

• Kawasaki disease (KD) is a leading cause of acquired pediatric cardiovascular disease.
• Coronary artery lesions are a major complication of KD, impacting long-term cardiac health.
• The molecular mechanisms underlying KD-associated coronary artery damage require further elucidation.

Purpose of the Study:

• To investigate the role of MEF2C in the pathogenesis of KD-associated coronary artery lesions.
• To explore the therapeutic potential of modulating MEF2C expression in KD.

Main Methods:

• Analysis of MEF2C expression in KD patients and human coronary artery endothelial cells (HCAECs).
• In vitro studies using HCAECs stimulated with KD serum to assess MEF2C's effect on inflammation and apoptosis.
• In vivo studies using a murine model of KD to evaluate the impact of MEF2C overexpression on coronary and cardiac function.
• RNA sequencing to identify downstream targets of MEF2C, including KLF2.

Main Results:

• MEF2C expression was downregulated in KD patients and in HCAECs during KD progression.
• Downregulated MEF2C correlated with increased inflammation and activated inflammatory pathways in KD.
• MEF2C overexpression reduced inflammation and apoptosis in HCAECs and protected against vascular and cardiac dysfunction in a KD mouse model.
• MEF2C protected against endothelial barrier disruption and KLF2 was identified as a key mediator of this protective effect.

Conclusions:

• MEF2C plays a critical protective role against KD-induced coronary artery injury.
• MEF2C mitigates inflammation, apoptosis, and endothelial barrier dysfunction in KD.
• MEF2C, potentially through KLF2, represents a promising therapeutic target for preventing and treating coronary lesions in Kawasaki disease.