Investigation of Induced Obstructive Sleep Apnea (OSA) in Rat Atria using Mass Spectrometry based Proteomics

• Published in: The FASEB journal Vol. 31; no. S1
• Main Authors: Channaveerappa, Devika, Lux, Jacob, Wormwood, Kelly L., McLerie, Meredith, Panama, Brian K., Darie, Costel C.
• Format: Journal Article
• Language: English
• Published: 01-04-2017
• DOI: 10.1096/fasebj.31.1_supplement.768.3
• EISSN: 1530-6860
• ISSN: 0892-6638

Abstract only Obstructive sleep apnea (OSA) affects up to 24% of the adult population and is associated with several atrial diseases. It is associated with daytime sleepiness, headache, depression, hypertension, obesity, arthritis, type 2 diabetes, and heart disease. OSA is characterized by transient cessations in respiration lasting >10 seconds as a result of narrowing or occlusion of the upper airway during sleep. OSA severity is assessed by the apnea‐hypopnea index (AHI), or the average number of apneas (complete obstructions) or hypopneas (partial obstructions) per hour. An estimated 20% of adults have mild OSA (AHI 5–15) and 7% of adults have moderate (AHI 15–30) to severe (AHI>30) OSA, with 85% of patients remaining undiagnosed. Although clinical evidence linking OSA to proarrhythmaic atrial changes is well known, the specific molecular mechanisms by which OSA causes atrial disease remain elusive. To study the OSA‐induced cardiac changes, we have initiated a recently developed rat model which closely recapitulates the characteristics of OSA. Male Sprague Dawley rats, aged 50–70 days, received surgically implanted tracheal balloons which were inflated to cause transient airway obstructions. Apnea groups experienced 60 apneas per hour of either 13 seconds (moderate apnea) or 23 seconds (severe apnea) for 2 weeks and 8 hours per day. Control rats received surgeries but no inflations. Proteomics analysis was done on the rat atria homogenates to identify dysregulated proteins in moderate and severe apnea when compared to control. SDS‐PAGE was performed on the homogenates to separate the proteins and the gel bands were trypsin digested to obtain the peptide mixtures. The peptides were analyzed by a Nano Acquity UPLC coupled with Xevo G2 Mass Spectrometer. Data analysis was done using ProteinLynx Global Server (PLGS 2.4), Mascot server and Scaffold 4.1 software. The proteomics analysis revealed that 3 of the 9 enzymes in glycolysis and 2 proteins related to oxidative phosphorylation were down‐regulated in the severe apnea group. In contrast, several structural and pro‐hypertrophic proteins were up‐regulated with chronic OSA. The data suggests the chronic OSA causes proteins changes which lead to cessation of glycolysis, a diminished capacity to generate reducing equivalents (i.e. NADH) as well as promotion of cardiac hypertrophy.
Support or Funding Information
Clarkson University