Transcriptomic analysis of cellular hypoxia response pathways in human endothelial cells

Abstract

Cellular adaptation to hypoxia involves complex transcriptional reprogramming mediated primarily through hypoxia-inducible factor signaling pathways. This research employed RNA sequencing to characterize the transcriptomic landscape of human endothelial cells exposed to hypoxic conditions, with particular focus on identifying novel regulatory networks and cell type-specific responses. Primary human umbilical vein endothelial cells and three additional endothelial cell types were cultured under hypoxic conditions (1% O2) for periods ranging from 2 to 48 hours at the Science for Life Laboratory facility in Uppsala. Differential expression analysis identified 2, 847 significantly altered transcripts, with 1, 623 upregulated and 1, 224 downregulated genes (FDR < 0.05, |log2FC| > 1). Pathway enrichment revealed predominant activation of glycolytic metabolism, angiogenesis, and autophagy pathways. Temporal analysis demonstrated distinct expression kinetics among HIF-target genes, with early-response genes (CA9, VEGFA) showing maximal induction at 24 hours while metabolic enzymes displayed sustained elevation. Cross-comparison between endothelial cell types revealed conserved core hypoxia responses with tissue-specific variations in magnitude. These findings provide comprehensive mapping of endothelial hypoxia responses with implications for understanding vascular adaptation in ischemic conditions.