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Mass Spectrometry based Proteomics Investigation of Induced Obstructive Sleep Apnea (OSA) in Rat Atria
Author(s) -
Darie Costel C,
Channaveerappa Devika,
Wormwood Kelly L.,
Lux Jacob,
Panama Brian
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb116
Subject(s) - obstructive sleep apnea , apnea , medicine , sleep apnea , cardiology , population , proteomics , airway , endocrinology , anesthesia , chemistry , biochemistry , environmental health , gene
Obstructive sleep apnea (OSA) affects up to 24% of the adult population and is associated with several atrial diseases. OSA is characterized by transient cessations in respiration lasting >10 seconds as a result of narrowing of the upper airway during sleep. An estimated 20% of adults have mild OSA and 7% of adults have moderate to severe 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. Methods 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 to separate the proteins and the peptide mixtures after trypsin digestion 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. Results Rats were given transient apneas for two durations: 13 and 23 s, we termed ‘moderate’ and ‘severe,’ respectively. These two apnea durations are within the range of those experienced by people with OSA. ECG recordings showed that the P wave durations (associated with left and right atrial depolarization) and T wave amplitudes (associated with ventricular repolarization) were increased by 2 weeks of chronic OSA. This was important since OSA patients show atrial electrical remodeling. The apnea model recapitulated the pathophysiological characteristics of OSA. 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 CAMP matching funds This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .