Patients with Obstructive Sleep Apnea Have Altered Levels of Four Cytokines Associated with Cardiovascular and Kidney Disease, but Near Normal Levels with Airways Therapy

Abstract

Introduction Obstructive sleep apnea (OSA) results in chronic intermittent hypoxia leading to systemic inflammation, increases in pro-inflammatory cytokines TNF-Alpha and IL-6, and increased risk for a number of life threatening medical disorders such as cardiovascular and kidney disease. Methods A BioPlex Array was used to examined the serum levels of four cytokines also expressed in endothelial cells and/or macrophages and associated with cardiovascular and kidney disease risk. Results Relative to untreated OSA patients, airways treated OSA patients had a 5.4-fold higher median level of MMP2 (p = 9.1x10 −11 ), a 1.4-fold higher level of TWEAK (p = 1.8x10 −7 ), a 1.7-fold higher level of CD163 (p = 1.4x10 −6 ), but a 2.0-fold lower level of MMP3 (p = 7.9x10 −7 ). Airway treatment resulted in levels more similar to or indistinguishable from control subjects. Both t-SNE or UMAP analysis of the global structure of these multi-dimensional data revealed two data clusters, one populated primarily with data for controls and most airways treated OSA patients and a second populated primarily with data for OSA patients. Discussion We discuss a concept in which the aberrant levels of these cytokines in untreated OSA patients may represent a chronic response after years of experiencing intermittent nightly hypoxia, which attenuated the acute response to hypoxia. A balanced therapeutic correction of the aberrant levels of these cytokines may limit the progression of CVD and kidney disease in OSA patients.

Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury

“…Wang et al [ 24 ] demonstrated that disturbances of genioglossal mitophagy are related to IH-induced mitochondrial morphology and function impairment, and supplementation of adiponectin can relieve the impairment via enhancing mitophagy. A two-way relationship between OSA and renal dysfunction has been proven in recent years [ 1 , 2 ]. As a novel pathophysiological feature of OSA, IH was demonstrated to be closely associated with renal impairment in experimental studies [ 7 – 10 , 25 – 28 ].…”

“…The relationship between obstructive sleep apnea (OSA) and renal dysfunction was found in recent years [ 1 , 2 ]. Especially, OSA can aggravate renal dysfunction in chronic renal diseases and vice versa [ 3 ].…”

Sleeping, Smoking, and Kidney Diseases: Evidence From the NHANES 2017–2018

“…A poor sleep profile or quality is another important risk factor of increasing CKDs risk (42). SA is a condition that has serious health consequences, has an increased risk of death, and is common in patients with CKDs (43,44) and DKD (45). Obstructive SA-related hypoxia causes several negative systemic effects, including oxidative stress (46,47), inflammation, and sympathetic activation, all of which contribute to the progression of renal disease.…”

Effects of Intermittent Hypoxia on Cytokine Expression Involved in Insulin Resistance

“…The relationship between IH and cytokine secretion has been reported not only in relation to insulin resistance and glucose intolerance, which is reviewed in this article, but also in relation to abnormal cytokine secretion associated with cardiovascular and renal diseases, nasal mucosal injury, and inflammation of the upper respiratory tract [34][35][36][37]. Since we previously investigated the way in which IH induces impaired insulin secretion/insulin resistance in in vitro experimental systems using pancreatic β cells, neuronal cells, hepatocytes, adipocytes, skeletal muscle cells, and cardiomyocytes [5,7,19,25,32,38], in this review, we focus on how IH induces insulin resistance.…”