Vasoactive Endothelial Growth Factor and Heat Shock Protein Gene Expression Response in Kawasaki Disease Associated Coronary Arteritis (preprint)

ABSTRACT

Background and Aim Coronary involvement in Kawasaki Disease (KD), whether its after SARS-CoV2 infection or not, can result in significant complications. There is the risk of aneurysm formation associated with inflammation and an unremitting fever. We wished to study the Vasoactive Endothelial Growth Factor (VEGF) and Heat Shock Response from a gene-expression perspective. Thereby aiming to furnish to insights that might be useful in the treatment of Kawasaki Disease. Method KD datasets based on previous work, were selected including microarray studies KD1 (GSE63881), KD2 (GSE73461), KD3 (GSE68004) and the RNAseq dataset KD4 (GSE64486) from the NCBI online repository. Based on clinical literature. HSP genes shown to be associated with angiogenesis were chosen for analysis as well as gene expression for VEFGA and VEGFB. Further in order to gain an impression of inflammatory patterns, gene expression for NFKB1 and TNF were also chosen. Tools for analysis included Gene Set Expression Analysis (GSEA). A KEGG pathway, outlining a relationship between VEGF and endothelial migration and proliferation was assumed. Results A KD dataset showed increased VEGFA and decreased VEGFB in acute versus convalescent samples. In all three KD datasets, HSPA1A and HSBAP1 genes were upregulated in acute versus convalescent samples. In KD4, cases of KD versus controls, VEGFB was down-regulated (p = 4.932e-02) and HSPBAP1 up-regulated (p = 1.202e-03). GSEA of KD1, KD2 and KD3, using Hallmark gene sets, suggested an inflammatory response with TNFA signaling via NFKB, IL6 JAK STAT 3 signaling, apoptosis, angiogenesis, and unfolded protein response. Conclusions A novel application of a model of VEGF and HSP to KD was presented. Coronary pathogenesis based on VEGF and HSP was explored. The ability to follow angiogenesis at the molecular level using a VEGF-HSP model may have therapeutic implications. Further, the significance of gene expression between VEGFA, VEGFB in KD and the relationship of HSP gene expression to angiogenesis in KD requires further study.