Ferroptosis-Related Oxidative Stress Activation in the Acute Phase of Kawasaki disease

Xing Xue¹Guangan Dai¹Yixiang Lin¹Lan He¹Wei Sheng¹Jingwei Sun²Fang Liu^1*

• ¹Heart Center, Children's Hospital of Fudan University, Shanghai, China
• ²Pediatrics Department, Bengbu First People's Hospital, Bengbu, China

Kawasaki disease (KD) is an acute systemic vasculitis with an unclear etiology and pathogenesis. Emerging evidence suggests a potential role of ferroptosis in various cardiovascular diseases. This study aimed to explore and validate the involvement of ferroptosis in the pathogenesis of KD. Peripheral blood samples from 10 patients with KD and 10 fever controls group (FC) were collected for RNA sequencing, which revealed significant enrichment of differentially expressed genes (DEGs) in the ferroptosis pathway. Validation of ferroptosis-related DEGs confirmed a trend toward ferroptosis activation in KD patients. In vitro, THP-1-derived macrophages (THP-1-Mφs) treated with serum from KD patients exhibited increased intracellular Fe²⁺ levels and lipid reactive oxygen species (ROS), impaired mitochondrial membrane potential, and characteristic mitochondrial morphological alterations associated with ferroptosis. Notably, these ferroptosis-related changes were attenuated by treatment with Liproxstatin-1, a specific ferroptosis inhibitor. In conclusion, our findings indicate that ferroptosis may contribute to the pathogenesis of KD and highlight ferroptosis inhibition as a potential therapeutic strategy for KD.