Elevated Monocytic Angiopoietin-2 Expression under Intermittent Hypoxia and in Patients with Obstructive Sleep Apnea

Abstract

Background: Angiopoietin-2 (Ang-2), a significant chemokine influencing monocyte chemotactic migration, was investigated under conditions of intermittent hypoxia and in obstructive sleep apnea (OSA) patients. This study aimed to elucidate the chemotactic impact of Ang-2 on monocytes during intermittent hypoxic conditions and to assess changes in the circadian concentration of Ang-2 in individuals with OSA. Methods: The OSA dataset GSE135917 was downloaded, and the Gene Set Enrichment Analysis (GSEA) method was employed to investigate the association between Ang-2 expression and potential signaling pathways in OSA. Monocytic THP-1 cells were utilized to examine the modulation of Ang-2 under intermittent hypoxia. Subsequently, the chemotactic motility of THP-1 cells was evaluated using a Transwell migration assay, and the number of migrating cells was quantified through flow cytometry. Monocyte RNA was isolated from peripheral venous blood obtained from 60 adult OSA patients and 60 healthy controls to conduct an Ang-2 mRNA expression study. Results: Bioinformatic analysis indicated that pathways significantly associated with high Ang-2 expression were predominantly enriched in extracellular regulated protein kinases (ERKs), phosphatidylinositol 3 kinase/serine-threonine kinase (PI3K/AKT), and nuclear factor kappa-B (NF-κB) signaling pathways. Experimental results demonstrated that intermittent hypoxia actively enhanced the expression of Ang-2 in monocytic THP-1 cells and facilitated the migration of THP-1 cells. Evidence suggested intermittent hypoxia induced the upregulation of Ang-2 expression via PI3K, ERKs, and NF-κB pathways. Additionally, Ang-2 expression in peripheral blood mononuclear cells was elevated in OSA patients, correlating with disease severity. Furthermore, Ang-2 mRNA expression in the OSA group was higher than in the control group. Conclusion: Ang-2 levels are elevated in OSA patients and are correlated with disease severity. Increased monocytic expression of Ang-2 is closely associated with intermittent hypoxia induced by OSA.