VEGF subtype A and B Gene Expression, Clues to a Temporal Signature in Kawasaki Disease, Implications for Coronary Pathogenesis through a Secondary analysis of Clinical Datasets.

Background and AimAn essential issue for Kawasaki Disease (KD) is the development of coronary artery disease. We decided to investigate (VEGF) subtype gene expression in KD due to the proangiogenic nature of Vasoactive Endothelial Growth Factor A (VEGF). VEGF-A is a known angiogenic molecule with pro-inflammatory effects, whereas the role of VEGFB has been less defined. MethodKD Microarray and RNA-seq datasets were selected using a comprehensive search strategy of the NCBI GEO Dataset, which resulted in eight studies from whole blood. This included three extensive studies in KD (KD1-KD3). Further, one study dataset from coronary artery tissue, the Coronary Artery Dataset (CAD), was also included to appreciate end-stage KD. ResultsIn CAD, cases of KD versus controls, VEGF-B was up-regulated (p = 4.932e-02). KD1, KD Acute versus convalescent samples, VEGF-A is up-regulated (p=1.258e-07) and VEGF-B was down-regulated (p=1.42e-28). Similar up regulation of VEGF-A and down regulation of VEGF-B was seen in KD2 (p=1.140e-04; p=1.746e-02) and KD3 (p=1.140e-04; p=1.746e-02), both are KD Versus Controls. VEGF-A up-regulated (p=1.140e-04), VEGF-B down-regulated (p=1.746e-02).KD3, KD versus Control; VEGF-A up-regulated (p=1.140e-04), VEGF-B down regulated (p=1.746e-02). ConclusionsIn acute KD VEGF-A up-regulation, with VEGFB being down-regulated, the reverse being true of the convalescent situation. This suggests a temporal inverse relationship between VEGF-A and VEGF-B may have biomarker implications. Moreover, a dual therapeutic strategy, enhancing VEGFB while minimizing VEGFA effects, could be a possible advancement over current KD related-therapies. Further work defining the relationship of VEGF-A to VEGF-B in KD-related angiogenesis is suggested.