A novel in vitro intermittent hypoxia-model reproduces the vascular endothelial transcriptional signatures of obstructive sleep apnea

ABSTRACT: Background: Vascular endothelial dysfunction (VED) is an early consequence of obstructive sleep apnea (OSA) and a precursor to hypertension and other cardiovascular diseases. Although the role of intermittent hypoxia (IH) in initiating endothelial injury is established, underlying molecular mechanisms remain unknown. This study aims to optimize an in vitro model that accurately simulates OSA effects on transcriptional endothelial alterations observed in OSA patients. Methods: A computationally modeled gas-controlled chamber was adapted to recreate intermittent hypoxia (IH) conditions experienced by the microcirculatory endothelium in OSA. Human microvascular endothelial cells (HMECs) were exposed to a 6-hour of IH (24 cycles/hour) with each cycle including 125 seconds of desaturation followed by 25 seconds of reoxygenation. Targeted gene expression, protein localization, and global transcriptomic changes were analyzed. Results: HMECs exposed to IH protocol showed no change inNFKB1 expression but significant upregulation of key genes associated with vascular pathology, including EDN1 (1.8-fold), NOX4 (1.7-fold), IL-8 (3.2-fold), and IL-1B (1.8-fold), recapitulating expression patterns observed in endothelial tissue of OSA patients. RNA-sequencing identified 904 differentially expressed genes, and Gene Ontology enrichment analysis showed significant activation of biological processes associated with hypoxia, angiogenesis, NF-KappaB and TGF-Beta signaling, endothelial remodeling, and suppression of mitocondrial function. Hallmark Gene Set Enrichment Analysis confirmed robust enrichment of TNF-alpha and TGF-Beta signaling and inflammatory response. Conclusion: This study, in addition to introducing a novel IH model, provides new mechanistic insight into endothelial pathways altered during acute IH and identifies biological processes that may contribute to the development of OSA-associated cardiovascular disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE348549 | GEO | 2026/09/29

REPOSITORIES: GEO