Endothelial Dysfunction In Obstructive Sleep Apnea Research Articles

Oral Vitamin C Supplementation and its Impact on Endothelial Function in Obstructive Sleep Apnea Patients

Background – Obstructive Sleep Apnea (OSA) is a prevalent condition associated with endothelial dysfunction, a precursor to cardiovascular disease. Passive Leg Movement (PLM) has emerged as a simple method to assess endothelial function. The role of oral vitamin C in improving endothelial function in OSA patients, however, has been underexplored. Materials and Methods This study recruited 26 male subjects, 13 with OSA and 13 healthy controls, aged 18-55 years. PLM was utilized to assess endothelial function by measuring femoral artery blood flow (FBF) and velocity (FBV) using Doppler ultrasound, pre- and post-administration of 1000mg of oral vitamin C. The intervention aimed to compare endothelial function responses between OSA patients and healthy controls, and to evaluate the impact of oral vitamin C on these responses. Results Baseline comparisons revealed a significant difference in FBF between OSA patients (76.6 ml/min) and healthy controls (162.1 ml/min, p < 0.05), indicating endothelial dysfunction in OSA. Post-vitamin C intervention, the peak FBF responses in OSA patients showed no significant difference (Pre-vitamin C: 76.6 ml/min, Post-vitamin C: 79.9 ml/min, p > 0.05), suggesting that oral vitamin C did not significantly improve endothelial function in OSA patients. Conclusion PLM effectively distinguished between healthy subjects and those with OSA through differences in FBF, confirming its utility as a diagnostic tool for endothelial dysfunction. However, oral vitamin C supplementation did not significantly enhance endothelial function in OSA patients, indicating the need for further research into alternative or adjunctive therapies.

The Association of Nephroblastoma Overexpressed (NOV) and Endothelial Progenitor Cells with Oxidative Stress in Obstructive Sleep Apnea.

Objective Obstructive sleep apnea (OSA) is a sleep disorder characterized by intermittent hypoxia, chronic inflammation, and oxidative stress and is associated with cardiometabolic disease. Several biological substrates have been associated with OSA such as nephroblastoma overexpressed (NOV), endothelial progenitor cells (EPC), and circulating endothelial cells (CEC). Few studies have looked at the association of NOV with OSA while the EPC/CEC relationships with OSA are unclear. In this study, we hypothesize that (1) NOV is associated with the severity of OSA independent of BMI, identifying a protein that may play a role in the biogenesis of OSA complications, and (2) EPCs and CECs are also associated with the severity of OSA and are biomarkers of endothelial dysfunction in OSA. Methods 61 subjects underwent overnight polysomnography (PSG), clinical evaluation, and blood analysis for NOV, EPC, CEC, interleukin 6 (IL-6), and other potential biomarkers. Results NOV and EPCs were independently associated with the oxygen desaturation index (ODI) after adjusting for potential confounders including body mass index (BMI), age, and sex (NOV p = 0.032; EPC p = 0.001). EPC was also independently associated with AHI after adjusting for BMI, age, and sex (p = 0.017). IL-6 was independently associated with AHI, but not with ODI. Conclusion NOV and EPC levels correlate with the degree of OSA independent of BMI, indicating that these biomarkers could potentially further elucidate the relationship between OSA patients and their risk of the subsequent development of cardiovascular disease.

Obstructive Sleep Apnea, oxidative stress, inflammation and endothelial dysfunction-An overview of predictive laboratory biomarkers.

Obstructive Sleep Apnea (OSA) represents an emerging public health concern with great impact on cardiovascular state. Oxidative stress (OS), inflammation and altered Nitric Oxide (NO) production are recognized as prominent mechanisms of many acute and chronic diseases and even of the normal aging process. They are investigated as major pathophysiological processes in OSA through the analysis and comparison of significative and validated biomarkers. The review is developed using as key terms "sleep apnea", "oxidative stress", "inflammation", and "endothelial dysfunction". Included studies must have followed the American Academy of Sleep Medicine guidelines according to the diagnosis and classification of OSA. Lipid, protein and DNA oxidation products, PCR, IL-6, IL-8, TNF-α, NO and nitrosative stress compounds, and endothelial functioning tests have been detected for their contribution in OSA along the last 3 decades. Nocturnal intermittent hypoxia has emerged to be significantly associated to oxidative/nitrosative stress, increase in pro-inflammatory markers, imbalance in NO production, and endothelium impairment. Body Mass Index (BMI) contribution needs further clarifications. Continuous Positive Airway Pressure (CPAP) therapy has demonstrated beneficial effects on vascular function and pro-inflammatory milieu in OSA. Oxidative stress and Inflammation significantly correlate with OSA; similarly, vascular functioning is impaired in accordance to unregulated levels of NO and derived compounds. Continuous Positive Airway Pressure markedly improves oxidative stress, inflammation and endothelial dysfunction in OSA.

Abstract 19768: eNOS Uncoupling Leads to Endothelial Dysfunction in Clinical Obstructive Sleep Apnea (OSA): Role of BH4 Depletion

OSA is increasingly recognized as a cardiovascular risk factor and is a cause of hypertension, worsening coronary disease and heart failure. OSA leads to endothelial dysfunction (ED) and decreased Nitric oxide (NO) availability. The mechanism of ED in OSA remains unknown. We previously found that OSA causes increased peroxynititrite production in the endothelium. We hypothesized that increased peroxynitrite would result in oxidative modification of proteins and decreased BH4 availability. Methods: Participants were 13 patients with recently diagnosed OSA and 10 healthy individuals with low cardiovascular risk. OSA Patients underwent subcutaneous forearm biopsy and doppler measurements of endothelial function by flow mediated dilation (FMD) prior to, and 12 weeks after initiation of treatment. Non-OSA controls also had FMD measurements and biopsies. NO and superoxide ( · O 2 _ ) levels in the microcirculation were determined using fluorescent probes CuFL and DHE respectively in the absence or presence of the NO synthase inhibitor, L-NAME, the NO scavenger, PTIO, and the SOD mimetic, MnTBAP. Results: OSA patients had impaired FMD, compared to non-OSA controls, which decreased after 12 weeks of CPAP treatment. OSA patients had increased endothelial · O 2 _ and decreased NO production compared to controls. CPAP treatment decreased · O 2 _ and increased NO production in OSA patients. Incubation of subcutaneous sections with BH4 resulted in a significant increase in NO and decrease in · O 2 _ production in the endothelial tissue of untreated OSA patients. The BH4 effect on · O 2 _ and NO was more in OSA patients before treatment than after treatment (Figure). This indicates BH4 deficiency is important for VED in OSA patients. Conclusions: Thus BH4 deficiency occurs in VED in OSA and BH 4 supplementation can restore eNOS function conferring protection with reduced oxidative stress. Future clinical studies are warranted to evaluate BH4 supplementation in normalization of ED in OSA.

Vascular Dysfunction in Sleep Apnea

See related article, pp 417–424 Cardiovascular disease remains one of the leading causes of morbidity and mortality. Obstructive sleep apnea (OSA) has been increasingly implicated in a breadth of cardiovascular diseases, including systemic hypertension, heart failure, stroke, arrhythmias, myocardial ischemia, and pulmonary arterial hypertension.1 The importance of this association, especially in the context of OSA as an etiologic factor, is compellingly relevant to disease management strategies, given the high prevalence of OSA and its likely rising trajectory secondary to the ongoing obesity epidemic.2 OSA may be present in approximately 20% of American adults, only a minority of whom have ever been diagnosed; this is true even for patients with established cardiovascular disease3 and despite the widespread availability of several effective treatment modalities (including continuous positive airway pressure [CPAP]). It is only over the past 2 decades that serious investigative interest has been paid to the interactions between OSA and cardiac and vascular disease and dysfunction. Deciphering the mechanisms, causal relationships, and potential therapeutic targets in the links between OSA and cardiovascular morbidity has not been an easy task, in part because of the constellation of comorbidities that characterize a large proportion of sleep apnea patients. OSA leads to multiple sources of cardiovascular stress, including nocturnal hypoxemia and hypercapnia, precipitous intrathoracic pressure changes, repetitive arousals, and poor sleep quality with consequent sleep deprivation. These, in turn, have been linked to endothelial dysfunction,4 systemic inflammation, sympathetic activation,5 metabolic dysregulation, hypercoagulability, and atrial enlargement, the combination of which may contribute to the initiation and progression of a range of cardiovascular diseases. Of these, endothelial dysfunction …

Mechanisms of endothelial dysfunction in obstructive sleep apnea

Endothelial activation and inflammation are important mediators of accelerated atherogenesis and consequent increased cardiovascular morbidity in obstructive sleep apnea (OSA). Repetitive episodes of hypoxia/reoxygenation associated with transient cessation of breathing during sleep in OSA resemble ischemia/reperfusion injury and may be the main culprit underlying endothelial dysfunction in OSA. Additional factors such as repetitive arousals resulting in sleep fragmentation and deprivation and individual genetic susceptibility to vascular manifestations of OSA contribute to impaired endothelial function in OSA. The present review focuses on possible mechanisms that underlie endothelial activation and inflammation in OSA.

Antioxidant Vitamin C Improves Endothelial Function in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is associated with oxidative stress, endothelial dysfunction, and increased cardiovascular morbidity and mortality. We tested the hypothesis that endothelial dysfunction in patients with OSA is linked to oxidative stress. In the present study, we measured flow-mediated dilation (FMD) of the brachial artery by ultrasound in 10 otherwise healthy, untreated patients with OSA and 10 age-and sex-matched control subjects without sleep-disordered breathing before and after intravenous injection of the antioxidant vitamin C. The investigator performing the FMD measurements was blinded to the status of the patients. When compared with control subjects, baseline FMD was significantly reduced in the patients with OSA. After intravenous injection of 0.5 g vitamin C, vasoreactivity remained unchanged in the control subjects. In the patients with OSA, ascorbate led to an increase in FMD to a level comparable to that observed in the control group. The reduced endothelial-dependent vasodilation in untreated patients with OSA acutely improves by the free radical scavenger vitamin C. These results are in favor of oxidative stress being responsible for the endothelial dysfunction in OSA. Antioxidant strategies should be explored for the treatment of OSA-related cardiovascular disease.