Khalyfa Abdelnaby, Gozal David
Department of Pediatrics, Biological Sciences Division, Pritzker School of Medicine, The University of Chicago, Chicago IL 60637, USA.
Department of Child Health, University of Missouri School of Medicine, Columbia, MO 65201, USA.
Curr Sleep Med Rep. 2018 Dec;4(4):300-311. doi: 10.1007/s40675-018-0130-7. Epub 2018 Oct 26.
To summarize the potential interactions between obstructive sleep apnea (OSA), atrial fibrillation (AF), and connexins.
OSA is highly prevalent in patients with cardiovascular disease, and is associated with increased risk for end-organ substantial morbidities linked to autonomic nervous system imbalance, increased oxidative stress and inflammation, ultimately leading to reduced life expectancy. Epidemiological studies indicate that OSA is associated with increased incidence and progression of coronary heart disease, heart failure, stroke, as well as arrhythmias, particularly AF. Conversely, AF is very common among subjects referred for suspected OSA, and the prevalence of AF increases with OSA severity. The interrelationships between AF and OSA along with the well-known epidemiological links between these two conditions and obesity may reflect shared pathophysiological pathways, which may depend on the intercellular diffusion of signaling molecules into either the extracellular space or require cell-to-cell contact. Connexin signaling is accomplished via direct exchanges of cytosolic molecules between adjacent cells at gap membrane junctions for cell-to-cell coupling. The role of connexins in AF is now quite well established, but the impact of OSA on cardiac connexins has only recently begun to be investigated. Understanding the biology and regulatory mechanisms of connexins in OSA at the transcriptional, translational, and post-translational levels will undoubtedly require major efforts to decipher the breadth and complexity of connexin functions in OSA-induced AF.
The risk of end-organ morbidities has initiated the search for circulating mechanistic biomarker signatures and the implementation of biomarker-based algorithms for precision-based diagnosis and risk assessment. Here we summarize recent findings in OSA as they relate to AF risk, and also review potential mechanisms linking OSA, AF and connexins.
总结阻塞性睡眠呼吸暂停(OSA)、心房颤动(AF)和连接蛋白之间的潜在相互作用。
OSA在心血管疾病患者中高度流行,与因自主神经系统失衡、氧化应激和炎症增加导致的终末器官严重发病风险增加相关,最终导致预期寿命缩短。流行病学研究表明,OSA与冠心病、心力衰竭、中风以及心律失常尤其是AF的发病率增加和病情进展有关。相反,AF在疑似OSA患者中非常常见,且AF的患病率随OSA严重程度增加而升高。AF与OSA之间的相互关系以及这两种疾病与肥胖之间众所周知的流行病学联系可能反映了共同的病理生理途径,这可能取决于信号分子在细胞间扩散到细胞外空间或需要细胞间接触。连接蛋白信号传导是通过间隙膜连接处相邻细胞之间直接交换胞质分子来实现细胞间偶联的。连接蛋白在AF中的作用现已得到充分证实,但OSA对心脏连接蛋白的影响直到最近才开始被研究。毫无疑问,要在转录、翻译和翻译后水平上理解连接蛋白在OSA中的生物学和调节机制,需要付出巨大努力来解读连接蛋白在OSA诱导的AF中的功能广度和复杂性。
终末器官发病风险促使人们寻找循环机制生物标志物特征,并实施基于生物标志物的算法进行精准诊断和风险评估。在此,我们总结了OSA与AF风险相关的最新发现,并回顾了连接OSA、AF和连接蛋白的潜在机制。