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

Wang, Ye; Meagher, Richard B; Ambati, Suresh; Cheng, Huimin; Ma, Ping; Phillips, Bradley G

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.