Abdelnaby Khalyfa1, David Gozal2. 1. Department of Pediatrics, Biological Sciences Division, Pritzker School of Medicine, The University of Chicago, Chicago IL 60637, USA. 2. Department of Child Health, University of Missouri School of Medicine, Columbia, MO 65201, USA.
Abstract
PURPOSE OF THE REVIEW: To summarize the potential interactions between obstructive sleep apnea (OSA), atrial fibrillation (AF), and connexins. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF THE REVIEW: To summarize the potential interactions between obstructive sleep apnea (OSA), atrial fibrillation (AF), and connexins. RECENT FINDINGS: 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. SUMMARY: 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.
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