Temporal Vascular Endothelial Growth Factor Sub-type gene Switching in SARS-CoV Pathogenesis. Interpretation through in vivo Murine C57BL Models

Abstract

Introduction: Increased Vascular Endothelial Growth Factor A (VEGF-A) levels are associated with Severe Acute Respiratory (SARS) infection. The aim was to investigate in vivo VEGF-A and VEGF-B (VEGF-A/B) gene expression (GE) in severe pulmonary disease pathogenesis. Method: Twelve temporal Mus musculus Wildtype (WT) C57BL/6 SARS-CoV MA15 lung studies were selected from the NCBI GEO database for GE profiling. Results: In murine dataset (GSE68820) Day 2 was compared to Day 7 demonstrating a downregulation trend in VEGF-A GE, with an opposite effect on VEGF-B GE (p=4.147e-03, p=7.580e-07, respectively). A v-shaped VEGF-B gene expression trajectory was noteworthy across certain datasets and after dORF6 stimulation. In addition, MA15 dose stimulation studies showed that a higher antigenic load caused more profound effects on VEGF-A resulting in a steeper fall in GE compared to other antigens. Conclusions: Distinct temporal trajectory patterns of VEGF-A and VEGF-B gene expression were associated with SARS-CoV MA15 stimulation. Unraveling the importance of VEG-A/B dynamics offers exciting prospects for improved bio-marking and therapeutic precision.