A dual covariant biomarker approach to Kawasaki disease, implications for coronary pathogenesis using vascular endothelial growth factor A and B gene expression; systematic secondary analysis of clinical datasets
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Informatics in Medicine Unlocked
Introduction Kawasaki disease (KD) is the most common vasculitis in young children, with coronary artery lesions (CALs) and coronary aneurysms (CAAs) being responsible for most KD-related deaths. Objective We hypothesized that Vascular Endothelial Growth Factors (VEGFs) are pivotal in KD inflammation and coronary artery lesions. This study assessed VEGF-A and VEGF-B gene expression (GE) as potential biomarkers in KD inflammation. Study design We analyzed NCBI-GEO datasets, categorizing gene expression patterns as "inflammatory" or "non-inflammatory". We focused on TNF-, NFKB1, VEGF-A, and VEGF-B GEs. Datasets were filtered based on differential changes in TNF and NFKB1 levels to isolate those with inflammatory shifts. Results Inflammatory datasets (GSE63881, GSE73464, and GSE68004) displayed elevated TNF, NFKB1, and VEGF-A GE levels during acute KD. VEGF-B GE exhibited a distinctive trend: an initial drop and subsequent rise during recovery, a pattern that was missing in the non-inflammatory group. The treatment response was also studied, with intravenous immunoglobulin (IVIG) responders showing significant downregulation of NFKB1 GE after treatment: GSE16797 [IVIG ± methylprednisolone; p = 8.6443-03], GSE48498 [IVIG; p = 6.618e-02, infliximab; p = 3.240e-03], and GSE18606 [IVIG; p = 3.518e-02]. Considering the similar binding of VEGF-A and VEGF-B to the VEGFR1 receptor, a co-variate and inverse relationship is suggested. Conclusion Temporal VEGF-A, VEGF-B, and GE changes show promise as new post-inflammatory biomarkers for KD. Novelty results with the biomarker approach, with the potential for a dual temporal relationship between VEGF-A and VEGF-A. A comprehensive exploration of VEGF-A and VEGF-B genes and protein analysis in KD is warranted to understand the functional aspects of these changes and how best to utilize the pattern of changes for therapeutic benefit.
Medicine and Health Sciences
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Rashid, Asrar; Benakatti, Govind; Al-Obeida, Feras; Phatak, Rajesh; Malik, Zainab A.; Sharief, Javed; Kadwa, Raziya; Hafez, Wael; Toufiq, Mohammed; Chaussabel, Damien; Malik, Rayaz; Quraishi, Nasir; Zaki, Syed Ahmed; Shaikh, Guftar; and Hussain, Amir, "A dual covariant biomarker approach to Kawasaki disease, implications for coronary pathogenesis using vascular endothelial growth factor A and B gene expression; systematic secondary analysis of clinical datasets" (2023). All Works. 6123.
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Gold: This publication is openly available in an open access journal/series