Endothelin-1 and LOX-1 as Markers of Endothelial Dysfunction in Obstructive Sleep Apnea Patients

Abstract

Introduction: The search of biochemical markers of endothelial dysfunction: lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)—involved in atherosclerotic plaques formation—and endothelin-1 (ET-1)—potent vasoconstrictor-might help in detecting obstructive sleep apnea (OSA) patients at high risk of cardiovascular diseases. Material and Methods: In 71 OSA patients (apnoea/hypopnoea index, AHI 28.2 ± 17.9/hour) and in 21 healthy controls the serum levels of LOX-1 and ET-1 were measured. Results: There were increased levels of ET-1 (1.58 ± 0.65 vs. 1.09 ± 0.38 pg/mL; p < 0.001) but not of LOX-1 in OSA patients as compared with healthy controls. In the patients’ group ET-1 levels negatively correlated with serum LDL levels. LOX-1 levels positively correlated with fasting glucose levels and were higher in the patients with than without diabetes. Neither ET-1 nor LOX-1 correlated with OSA severity. In mild OSA patients, there was a negative correlation between LOX-1 and mean arterial oxygen saturation during sleep. In severe OSA patients, there was a positive correlation between LOX-1 levels and uric acid. Conclusion: There is endothelial dysfunction in OSA patients as indicated by increased serum levels of ET-1 and possibly endothelial dysfunction in diabetic OSA patients as indicated by increased serum levels of LOX-1 and its correlation with fasting glucose levels.

Oxidative Stress, Kinase Activation, and Inflammatory Pathways Involved in Effects on Smooth Muscle Cells During Pulmonary Artery Hypertension Under Hypobaric Hypoxia Exposure

“…ET-1 is produced primarily by endothelial cells but can also be secreted by epithelial cells, macrophages, and fibroblasts. Importantly, studies have shown that SMCs can also produce ET-1 ( Yanagisawa et al, 1988 ; Miller et al, 1993 ; Kosacka and Brzecka, 2021 ). The activity of ET-1 is increased in hypoxia; this increase is related to the level of HIF-1, since ET-1 contains a HIF-1 binding site at base pair 118 ( Yamashita et al, 2001 ).…”

The Role of IL-6 and ET-1 in the Diagnosis of Coronary MicroVascular Disease in Women

“…The pathophysiological mechanisms of OSA involved in ischemic coronary heart disease are represented by chronic activation of the sympathetic system, oxidative stress, endothelial dysfunction, and chronic inflammation. [ 31 , 32 ]. Therefore, the levels of markers, such as CRP, TNF-alpha, IL-6, IL-8, but also that of ET1, are increased, and all being strongly involved in the pathogenesis of atherosclerotic disease.…”

“…Therefore, the levels of markers, such as CRP, TNF-alpha, IL-6, IL-8, but also that of ET1, are increased, and all being strongly involved in the pathogenesis of atherosclerotic disease. A recently published study, which evaluated the correlation between serum levels of ET-1 and LOX-1(lectin-like oxidized low-density lipoprotein receptor-1), both being involved in the atherosclerotic process, in patients with sleep apnea syndrome and the risk of cardiovascular adverse events, demonstrated a direct relationship between the presence of sleep apnea syndrome and the level of ET-1 and, consequently, a higher cardiovascular risk [ 32 ]. Indeed, we did not analyze the prevalence of OSA among the obese patients included in the study, but there is a high probability that they also hide this respiratory pathology, which accentuates inflammation and endothelial dysfunction and implicitly the atherosclerotic process.…”

Obstructive Sleep Apnea Syndrome: From Symptoms to Treatment

“…Bosi et al [ 5 ] developed a qualitative pathophysiological classification (PALM grades) by means of clinical PSG, grade of OSA severity, and therapeutic level of continuous positive airway pressure (CPAP). All of these data are a solid base for the pre-operative surgical assessment, the therapeutic recommendations, and their potential outcomes and side effects [ 10 , 11 , 12 , 13 , 14 , 15 ]. Drug-induced sleep endoscopy (DISE) represents another method for evaluating sites and patterns of collapse in OSA patient candidates to surgical treatment.…”

“…It consists in an upper airway evaluation during a pharmacologically simulated sleep. Yu Lin et al [ 15 ] and other literature evidence [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ] has stated that DISE is superior to the wake-up endoscopy in identifying obstructions sites and types of collapses in the hypopharyngeal and base of the tongue regions. Recently, the use of a middle latency auditory evoked potentials (MLAEP) has been proposed as a good methodology to evaluate the correct level of sedation for patients during DISE procedures [ 16 , 17 ].…”