Channaveerappa Devika, Lux Jacob C, Wormwood Kelly L, Heintz Timothy A, McLerie Meredith, Treat Jacqueline A, King Hannah, Alnasser Donia, Goodrow Robert J, Ballard Glenn, Decker Robert, Darie Costel C, Panama Brian K
Biochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, USA.
Department of Experimental Cardiology, Masonic Medical Research Laboratory, Utica, NY, USA.
J Cell Mol Med. 2017 Sep;21(9):2223-2235. doi: 10.1111/jcmm.13145. Epub 2017 Apr 12.
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.
阻塞性睡眠呼吸暂停(OSA)影响9%至24%的成年人口。OSA与心房疾病有关,包括心房扩大、纤维化和心律失常。尽管OSA与心脏病之间存在联系,但OSA时心脏发生的分子变化仍不清楚。为了研究OSA引起的心脏变化,我们利用了一种最近开发的大鼠模型,该模型密切模拟了OSA的特征。50至70日龄的雄性Sprague Dawley大鼠接受手术植入气管球囊,球囊充气以引起短暂气道阻塞。大鼠每小时接受60次呼吸暂停,每次13秒(中度呼吸暂停)或23秒(重度呼吸暂停),每天8小时,持续2周。对照组接受植入物,但不进行充气。定期进行脉搏血氧饱和度测量,并记录呼吸暂停后的心电图。慢性OSA后大鼠的P波持续时间延长,T波振幅增加。心房组织匀浆的蛋白质组分析显示,重度呼吸暂停组中糖酵解的九种酶中的三种以及与氧化磷酸化相关的两种蛋白质表达下调。一些肌节蛋白和促肥厚蛋白也随着OSA上调。慢性OSA导致心房蛋白质变化,提示能量代谢受损和肥厚增强。