Plasma proteomic profiling reveals that SERPINE1 is a potential biomarker associated with coronary artery lesions in Kawasaki disease

Background: Kawasaki disease (KD) is the most common cause of acquired heart disease in childhood. Coronary artery lesions (CALs) are serious complications of KD that can result in stenosis and thrombosis, but the specific underlying pathogenic mechanisms have not been elucidated. Therefore, exploring biomarkers to help predict early CALs is urgently needed for clinical treatment. Methods: Patients were recruited from three independent cohorts. In the discovery cohort, Data-Independent Acquisition Mass Spectrometry (DIA-MS) was performed to screen plasma proteins from healthy controls (HCs), KD patients prior to intravenous immunoglobulin (IVIG) treatment, and KD patients post-IVIG treatment. KD patients were further divided into KD patients without CALs (nCAL) and with CALs (CALs) groups. Bioinformatic analysis was carried out for the differentially expressed proteins (DEPs) and hub proteins. Candidate proteins were quantified by enzyme-linked immunosorbent assay (ELISA) in the validation cohort 1 and 2. Furthermore, candida albicans cell wall extract (CAWS)-induced KD vasculitis mice and cell models were established to investigate the expression of biomarkers identified in the aforementioned clinical cohort. Results: According to the quantitative proteomics analysis, SERPINE1 was significantly increased in KD patients with CALs. Receiver operating characteristic curves (ROC) revealed that plasma SERPINE1 exhibited greater ability in predicting CALs (AUC = 0.824, P < 0.0001). After IVIG treatment, the concentrations of SERPINE1 in the nCALs group significantly decreased. However, the concentration of SERPINE1 remained persistently elevated in the CALs group. Moreover, the expression of SERPINE1 was significantly upregulated in the heart tissue of KD mice, KD plasma, or tumor necrosis factor-alpha (TNF-alpha)-stimulated human coronary artery endothelial cells (HCAECs). Conclusions: Overall, our results suggest that the plasma concentration of SERPINE1 might serve as a new potential predictive biomarker for CALs in KD patients.