Atrial electrophysiological and molecular remodelling induced by obstructive sleep apnoea

Abstract

Obstructive sleep apnoea (OSA) affects 9–24% of the adult population. OSA is associated with atrial disease, including atrial enlargement, fibrosis and arrhythmias. Despite the link between OSA and cardiac disease, the molecular changes in the heart which occur with OSA remain elusive. To study OSA‐induced cardiac changes, we utilized 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. Rats were given 60 apnoeas per hour of either 13 sec. (moderate apnoea) or 23 sec. (severe apnoea), 8 hrs per day for 2 weeks. Controls received implants, but no inflations were made. Pulse oximetry measurements were taken at regular intervals, and post‐apnoea ECGs were recorded. Rats had longer P wave durations and increased T wave amplitudes following chronic OSA. Proteomic analysis of the atrial tissue homogenates revealed that three of the nine enzymes in glycolysis, and two proteins related to oxidative phosphorylation, were down regulated in the severe apnoea group. Several sarcomeric and pro‐hypertrophic proteins were also up regulated with OSA. Chronic OSA causes proteins changes in the atria which suggest impairment of energy metabolism and enhancement of hypertrophy.

Identification of dysregulation of atrial proteins in rats with chronic obstructive apnea using two‐dimensional polyacrylamide gel electrophoresis and mass spectrometry

“…The rats and the rat model setup ( Figure S1) and the sample preparation method used in this study was described previously. 3,6 Atrial homogenates of control (n = 2), moderate (n = 2) and severe (n = 2) apnea were analysed by 2D PAGE and nanoLC-MS/MS analysis. A total of 2293 protein spots were compared for statistical differences, of which 208 spots having a fold increase or decrease of ≥1.7 and a P ≤ 0.05, or a fold increase or decrease of ≥3.0 were selected for nanoLC-MS/MS analysis, as previously described.…”

“…1,2 Although OSA has been closely associated with atrial arrhythmia, atrial enlargement, increased P wave duration and decreased atrial voltage; little is known about the molecular pathways causing these pathologies. 3,4 Many animal models do not address both the obstructive and hypoxemic components of OSA in conscious, free roaming animals. In order to accurately reproduce the effects of OSA as observed in the clinic, we have employed a surgical model involving a silicone obstructive device implanted in the trachea of conscious, free roaming rats.…”

Proteomic Analysis of the Lake Trout (Salvelinus namaycush) Liver Identifies Proteins from Evolutionarily Close and ‐Distant Fish Relatives

“…All 62 samples from the liver were analyzed by nanoLC‐MS/MS using a nanoAcquity UPLC (Waters Corp, Milford, MA) coupled to a Q‐TOF Xevo G2 (Waters Corp, Milford, MA) according to published procedures . The peptides were loaded onto a 150 mm x 100 mm nanoAcquity BEH130 C18 1.7 um UPLC column (Waters, Milford, MA) and eluted over a 150‐min gradient at a flow rate of 400 nL min −1 .…”

“…Raw data files were converted to peak list files using Protein Links Global Server 2.4 (PLGS 2.4, Waters Corp, Milford, MA) . The following parameters were used: background subtraction of polynomial order 5 adaptive, a threshold of 30%, two smoothings with a window of three channels in Savitzky–Golay mode, and centroid calculation of top 80% of peaks based on a minimum peak width of four channels at half height.…”

Identification of dysregulation of atrial proteins in rats with chronic obstructive apnea using twodimensional polyacrylamide gel electrophoresis and mass spectrometry

“…OSA has been associated with headache, daytime sleepiness, obesity, depression, arthritis, type 2 diabetes mellitus, arteriosclerosis, atherosclerosis, hypertension, atrial arrhythmia, and sudden cardiac death [1,2]. Although OSA has been closely associated with atrial arrhythmia, atrial enlargement, increased P wave duration, and decreased atrial voltage; little is known about the molecular pathways causing these and other pathologies [4][5][6]. Many animal models do not address both the obstructive and hypoxemic components of OSA in conscious, free roaming animals.…”