The Impact of Intermittent Hypoxemia on Left Atrial Remodeling in Patients with Obstructive Sleep Apnea Syndrome

Abstract

Obstructive sleep apnea syndrome (OSAS) is a significant risk factor for left atrial (LA) remodeling. Intermittent hypoxemia occurs during the sleep cycle in patients with OSAS and plays a crucial role in cardiovascular pathologies such as stroke, arrhythmia, and coronary artery disease. However, there is very little information about the role of intermittent hypoxemia in LA remodeling in patients with OSAS. In total, 154 patients with sleep-related breathing disorders (SRBD) were prospectively recruited for this study. All enrolled SRBD patients underwent polysomnography and echocardiography. Significant OSAS was defined as an oxygen desaturation index (ODI) of ≥10 per hour. Intermittent hypoxia/reoxygenation (IHR) stimulation was used to test the effect of hypoxia on the viability, reactive oxygen species, apoptosis, and inflammation-associated cytokine expression in the HL-1 cell line. To investigate the effect of patients’ exosomes on HIF-1 and inflammation-associated cytokine expression, as well as the relationship between ODI and their expression, exosomes were purified from the plasma of 95 patients with SRBD and incubated in HL-1 cells. The LA size was larger in patients with significant OSAS than in those without. There was a significant association between ODI, lowest SpO2, mean SpO2, and LA size (all p < 0.05) but not between the apnea–hypopnea index and LA size. IHR condition caused increased LDH activity, reactive oxygen species (ROS) levels, and apoptosis in HL-1 cells and decreased cellular viability (all p < 0.05). The expression of HIF-1α, TNF-α, IL-6, and TGF-β increased in the IHR condition compared with the control (all p < 0.05). The expression of HIF-1α, IL-1β, and IL-6 increased in the HL-1 cells incubated with exosomes from those patients with significant OSAS than those without (all p < 0.05). There was a significantly positive correlation between ODI and the expression of HIF-1α, TNF-α, IL-1β, IL-6, and TGF-β; a significantly negative correlation between mean SpO2 and IL-6 and TGF-β; and a significantly negative correlation between the lowest SpO2 and HIF-1α (all p < 0.05). In conclusion, intermittent hypoxemia was strongly associated with LA remodeling, which might be through increased ROS levels, LDH activity, apoptosis, and the expression of HIF-1α and inflammation-associated cytokines.

Periostin and TNF-α expression levels in peripheral blood of patients with acute cerebral infarction combined with obstructive sleep apnea syndrome and their predictive value for clinical prognosis

“…The results of this study showed that peripheral blood TNF-α levels were significantly elevated in patients with ACI combined with OSAS and were positively correlated with the NIHSS and mRS scores, indicating that inflammation was aggravated by the occurrence of ACI and OSAS. In addition, intermittent hypoxia/reoxygenation (IHR) can also activate the TLR4/NF-κB signalling pathway, leading to inflammation and thus the upregulation of TNF-α, a downstream inflammatory factor [ 23 ]. TNF-α induces the expression of periostin through the transcription factor c-Jun [ 24 ], which is consistent with the results of the present study, in which Pearson correlation analysis showed that periostin was significantly positively correlated with TNF-α.…”

Mechanisms of Atrial Fibrillation in Obstructive Sleep Apnoea

“…Thus, CIH drives an imbalance between collagen secretion and degradation. CIH may also contribute to atrial remodelling by promoting inflammatory myocardial apoptosis [ 69 , 78 ]. These processes are summarised in Figure 1 .…”

“…This implies a reactive oxygen species (ROS)-dependent remodelling process, either by direct protein oxidation or secondary cell signalling processes. Indeed, markers of oxidative stress are elevated in numerous OSA models [ 56 , 57 , 78 , 79 ]. This is a prominent feature of CIH, as ROS are cyclically produced with intermittent re-oxygenation in a fashion similar to ischaemia–reperfusion injury [ 81 ].…”

“…Besides ROS signalling, hypoxia-inducible factor (HIF)-1α is known to play an important role in hypoxia sensing. Animal and cellular CIH models have demonstrated upregulations of HIF-1α with apoptosis, fibrosis, and inflammation [ 42 , 78 ]. Furthermore, serum HIF-1α is significantly upregulated in patients with OSA and may be useful as a biomarker of OSA severity [ 82 , 83 ].…”

Recent trends in the nanozeolites-based oxygen concentrators and their application in respiratory disorders

“…This pure or concentrated oxygen is indeed known as medical oxygen, and in the absence of it, a patient may experience hypoxemia [low levels of oxygenated blood ( 3 )]. Hypoxemia is caused by a range of common conditions—including childhood pneumonia, newborn conditions ( 4 , 5 ), and obstetric emergencies ( 6 , 7 ). The body of the sufferer will experience severe detrimental consequences from hypoxemia on the cells that carry out crucial biological functions ( 8 ).…”