Abstract
BackgroundObstructive sleep apnea (OSA) is known to be a risk factor of coronary artery disease. The chemotaxis and adhesion of monocytes to the endothelium in the early atherosclerosis is important. This study aimed to investigate the effect of intermittent hypoxia, the hallmark of OSA, on the chemotaxis and adhesion of monocytes.MethodsPeripheral blood was sampled from 54 adults enrolled for suspected OSA. RNA was prepared from the isolated monocytes for the analysis of C-C chemokine receptor 2 (CCR2). The effect of intermittent hypoxia on the regulation and function of CCR2 was investigated on THP-1 monocytic cells and monocytes. The mRNA and protein expression levels were investigated by RT/real-time PCR and western blot analysis, respectively. Transwell filter migration assay and cell adhesion assay were performed to study the chemotaxis and adhesion of monocytes.ResultsMonocytic CCR2 gene expression was found to be increased in severe OSA patients and higher levels were detected after sleep. Intermittent hypoxia increased the CCR2 expression in THP-1 monocytic cells even in the presence of TNF-α and CRP. Intermittent hypoxia also promoted the MCP-1-mediated chemotaxis and adhesion of monocytes to endothelial cells. Furthermore, inhibitor for p42/44 MAPK or p38 MAPK suppressed the activation of monocytic CCR2 expression by intermittent hypoxia.ConclusionsThis is the first study to demonstrate the increase of CCR2 gene expression in monocytes of severe OSA patients. Monocytic CCR2 gene expression can be induced under intermittent hypoxia which contributes to the chemotaxis and adhesion of monocytes.
Highlights
Obstructive sleep apnea (OSA), defined as repeated episodes of obstructive apnea and hypopnea during sleep, together with symptoms of daytime sleepiness or frequently altered cardiopulmonary function, affects at least 5% of the general population [1,2]
Patients recruited in this study were divided into four groups according to the severity of OSA as indicated by apnea-hypopnea index (AHI), an index used to assess the severity of sleep apnea based on the total number of complete cessations and partial obstructions of breathing occurring per hour of sleep
The monocytic chemokine receptor 2 (CCR2) mRNA expression was found to be gradually increased along the severity of these OSA patients in the group with Apnea-hypopnea index (AHI) .30 which was statistically significant when compared with three other groups
Summary
Obstructive sleep apnea (OSA), defined as repeated episodes of obstructive apnea and hypopnea during sleep, together with symptoms of daytime sleepiness or frequently altered cardiopulmonary function, affects at least 5% of the general population [1,2]. OSA results in intermittent hypoxia (IH) and sleep fragmentation with neurocognitive dysfunction and cardiovascular disease as the major sequelae [3]. Previous studies report that patients with sleep apnea have an increased risk of diurnal hypertension, nocturnal dysrhythmias, pulmonary hypertension, right and left ventricular failure, myocardial infarction and stroke, suggesting that sleep apnea may be one of the important risk factors of cardiovascular disorders [4,5]. Possible mechanisms responsible for the development of those cardiovascular sequelae from OSA include intermittent hypoxia and hypercapnia, exaggerated negative intrathoracic pressure and bursts of sympathetic activity, which provoke surges in blood pressure and result in endothelial cell dysfunction [10,11]. Obstructive sleep apnea (OSA) is known to be a risk factor of coronary artery disease. This study aimed to investigate the effect of intermittent hypoxia, the hallmark of OSA, on the chemotaxis and adhesion of monocytes
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