Upper airway microcirculation remodeling in obstructive sleep apnea is not driven by endothelial activation

Microcirculation contributes significantly to blood flow resistance, with upper airway microcirculation in obstructive sleep apnea (OSA) affected by endothelial activation, perturbed blood flow shear stress, and snoring-induced tissue vibration. The relevance of these mechanisms on microcirculation response and remodeling remains largely unknown but may influence management decisions in OSA. This study analyzed pharyngeal muscle tissue from non-obese, young adult patients with OSA and chronic heavy snoring. We assessed arteriole morphometry and quantified the expression of endothelial activation markers: 8-isoprostane, vascular cell adhesion molecule-1, E-selectin, vascular endothelial growth factor, endothelin-1, and endothelial cell specific molecule-1. Morphometric analysis of 319 arterioles (mean of 8 vessels per patient) revealed thicker walls in severe OSA compared to mild OSA without lumen reduction, indicating outward hypertrophy, and a positive correlation between the apnea-hypopnea index (a measure of OSA severity) and arteriole wall thickness. However, analysis of 1872 arterioles showed no increase in endothelial activation markers with disease severity, either in the arteriole walls or muscle tissue. This suggests that, in young non-obese adults, severe OSA likely leads to adaptive, mechanically driven microcirculation outward hypertrophy, potentially due to perturbed shear stress, with potential implications for OSA management.