Endothelial Glycocalyx Injury in Obstructive Sleep Apnea Links Repetitive Hypoxemia to Immunothrombotic Endothelial Dysfunction

ABSTRACT: BACKGROUND: Obstructive sleep apnea (OSA) is associated with cardiovascular disease. The endothelial glycocalyx (eGCX) is a shear-sensitive, interfacial barrier towards the intravascular compartment. The relevance of OSA and intermittent hypoxia (IH) for eGCX injury and, subsequently, cardiovascular pathologies in humans remains unclear. METHODS: In a prospective, single-center observational study in men, polysomnography quantified apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and hypoxic burden (HB). Plasma levels of the key eGCX glycosaminoglycans hyaluronan (HA) and heparan sulfate (HS) and the proteoglycan syndecan-1 (SDC-1) were related to OSA severity and repetitive hypoxemia. Plasma proteomics defined pathways associated with OSA and an HA/HS-derived eGCX score. In parallel, shear-matured primary human endothelial cells were exposed to OSA-characteristic IH cycles under arterial flow to assess eGCX structure, oxidative stress, nitric-oxide (NO) signaling, thromboinflammatory status, and to test N-acetylcysteine as an antioxidant. RESULTS: Plasma levels of HA and HS were higher in OSA than in non-OSA individuals and increased stepwise with disease severity, tracking AHI, ODI and HB. Plasma SDC-1 did not differ between the groups. Proteomics revealed enrichment of inflammation, coagulation, and oxidative stress-related pathways that strengthened with increasing OSA burden and higher eGCX scores. Experimentally, IH caused loss of endothelial surface HA/HS with increased shedding, increased reactive oxygen species, reduced redox capacity, and decreased endothelial NO synthase expression and NO bioavailability. IH or enzymatic eGCX digestion each enhanced monocyte adhesion and fibrin deposition on the endothelium under physiological shear, while N-acetylcysteine attenuated oxidative stress and partially restored surface HA expression. CONCLUSIONS: Integrated patient and IH-model data indicate that OSA is associated with eGCX degradation linked to oxidative-inflammatory stress and a pro-adhesive, pro-thrombotic endothelial phenotype. These data highlight circulating HA and HS as translational biomarkers of OSA-related eGCX injury with potential utility for risk stratification and as pharmacodynamic readouts for eGCX-stabilizing adjunct therapies.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Teresa Barth  

LAB HEAD: Martin Bernhard Mueller

PROVIDER: PXD073409 | Pride | 2026-06-29

REPOSITORIES: Pride