A pilot study on the effect of severe sleep fragmentation on aorta remodelling, neuroinflammation in a rat model.

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). Currently, the potential role of SF has not been extensively explored with animal models and it remains unclear to what extent recurring arousals and sleep disruption that characterize sleep fragmentation in OSA contribute to an early cardiovascular dysfunction. To determine early changes in cardiovascular anatomy, we set up studies with a middle-aged rat model of SF exposed for 1 month. We evaluated biomechanical responses parameters such as elasticity, histomorphological changes, inflammation, oxidative stress, and blood serum molecule extracellular vesicles in a population exposed to such SF compared to a control group. Our experiments enabled us to show that 30 days of SF normoxia in adult rats induced aortic remodeling, with an increase in diameter of thoracic aortas and fiber disorganization associated with an increase in biomechanical elasticity as well as slight alterations in blood serum biomarkers. An increase in extracellular vesicles content of CD31 was observed in SF rats. Matrix metalloproteinases-9 (MMP9) has also been identified as a potential remodeling biomarker linked to aortic elasticity. We observed an increase in release of MMP9 in our model, the same way as we obtained an increase in ox-LDL that is another oxidative stress marker associated with atherosclerosis. Our preliminary findings support that SF alters aortic function, structure and biomechanical properties and release extracellular vesicles; and therefore these should be considered in preventive cardiovascular health programs.