Identification of Cardiovascular Biomarkers in a Rat Model of Obstructive Sleep Apnea
Dong-Ick Shin1, Ho-seong Han2
1Neurology, Chungbuk National University Hospital, Chungbuk National University, 2Neurology, Yuseong Sun General Hospital
Objective:
Our study aims to identify specific cardiovascular biomarkers associated with OSA using a rat model. 
Background:
Obstructive sleep apnea (OSA) has emerged as a recognized risk factor for cardiovascular disease. We investigate miRNA expression patterns and gene expression changes related to cardiovascular disease, shedding light on the neurologic implications of this critical intersection between sleep disorders and cardiovascular health.
Design/Methods:

We induced OSA in a rat model by administering hyaluronic acid-based filler (0.1 mL/100 g body weight) at the base of the tongue. Blood pressure measurements were obtained using the CODA-NIBP system at 22 and 44 weeks post-OSA induction. Polysomnographic assessments were performed to gauge the similarity of the rat model to human OSA. Expression profiles of miRNAs and mRNAs were analyzed using the GeneChip rat gene ST 2.0 and Affymetrix miRNA 4.0 microarrays, respectively.

Results:

Our OSA rat model exhibited clinical similarities to human OSA, including elevated apnea-hypopnea and oxygen desaturation indices. We observed increased blood pressure, left ventricular hypertrophy, and systemic arterial changes. Gene expression analysis revealed alterations associated with cardiovascular diseases such as atherosclerosis and myocardial injury. Notably, miRNA profiling identified miR-23a-5p and miR-375-3p linked to endothelial dysfunction, myocardial injury, inflammation, apoptosis, and atherosclerosis.

Conclusions:

Our study efficiently replicates the cardiovascular implications of human OSA in a rat model, revealing structural and functional changes within the cardiovascular system. We unveil two significant biomarkers, miR-23a-5p and miR-375-3p, with concurrent increases in both blood and systemic arteries. These findings contribute to our understanding of the pathophysiological mechanisms underlying OSA-related cardiovascular complications, with potential neurologic implications.

10.1212/WNL.0000000000204515