Aortic remodelling induced by obstructive apneas is normalized with mesenchymal stem cells infusion.
Cira RubiesAna-Paula DantasMontserrat BatlleMarta TorresRamon FarreGemma SangüesaJosep M MontserratLluis MontIsaac AlmendrosEduard GuaschPublished in: Scientific reports (2019)
Obstructive sleep apnea syndrome (OSA) promotes aortic dilatation, increased stiffness and accelerated atherosclerosis, but the mechanisms of vascular remodelling are not known. We aimed to assess vascular remodelling, its mechanisms, and the effect of mesenchymal stem cells (MSC) infusions in a clinically relevant rat model of chronic OSA involving recurrent airway obstructions leading thoracic pressure swings and intermittent hypoxia/hypercapnia (OSA-rats). Another group of rats were placed in the same setup without air obstructions (Sham-rats) and were considered controls. Our study demonstrates that chronic, non-invasive repetitive airway obstructions mimicking OSA promote remarkable structural changes of the descending thoracic aorta such as eccentric aortic hypertrophy due to an increased wall thickness and lumen diameter, an increase in the number of elastin fibers which, in contrast, get ruptured, but no changes in tunica media fibrosis. As putative molecular mechanisms of the OSA-induced vascular changes we identified an increase in reactive oxygen species and renin-angiotensin system markers and an imbalance in oxide nitric synthesis. Our results also indicate that MSC infusion blunts the OSA-related vascular changes, most probably due to their anti-inflammatory properties.
Keyphrases
- obstructive sleep apnea
- positive airway pressure
- mesenchymal stem cells
- aortic valve
- pulmonary artery
- sleep apnea
- reactive oxygen species
- left ventricular
- spinal cord
- aortic dissection
- umbilical cord
- magnetic resonance
- drug induced
- type diabetes
- bone marrow
- stem cells
- heart failure
- clinical trial
- endothelial cells
- oxidative stress
- pulmonary hypertension
- computed tomography
- body composition
- resistance training
- high intensity
- stress induced
- brain injury