Key Regulatory Effect of Activated HIF-1α/VEGFA Signaling Pathway in Systemic Capillary Leak Syndrome Confirmed by Bioinformatics Analysis

Abstract

Systemic capillary leak syndrome (SCLS) is a rare disorder characterized by capillary leakage of plasma fluids throughout the endothelium. The mechanism of SCLS is still unknown. Vascular endothelial growth factor (VEGF), an inducer or barrier disruption, is markedly upregulated in SCLS. This study was to investigate the molecular mechanisms involving SCLS-related inflammation and neuron damage in SCLS remain unclear. Data files of GSE97287 dataset were extracted and processed for identification of differentially expressed genes (DEGs), including upregulated adrenomedullin (ADM) gene, hypoxia-inducible factor-1α (HIF-1α) and VEGFA; and downregulated aldehyde dehydrogenase 1A1 (ALDH1A1) gene and interleukin (IL)-2 receptor β (IL-2RB) gene. Weighted gene coexpression network analysis (WGCNA) was performed for DEGs and four significant modules were identified and were enriched Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to immune response, angiogenesis, neuroblast proliferation, HIF-1 signaling pathway, and Parkinson's disease. The activated HIF-1α/VEGFA signaling in SCLS patients might well be responsible for the impaired inflammatory, nervous, and immune systems.