Activation of inflammatory circulating factors by intermittent hypoxia in sleep apnea syndrome

Abstract

Obstructive sleep apnea syndrome (OSAS), characterized by intermittent and recurrent pauses in respiration during sleep, constitutes an independent risk factor for cardiovascular morbidity. Intermittent hypoxia (IH) is the hallmark of OSAS. A large number of clinical studies, cell culture, and animal models utilizing IH delineate the central role of oxidative stress in OSAS. These facilitate increased interactions of blood leukocytes with endothelial cells, resulting in endothelial injury and dysfunction. Such events can promote the development of cardiovascular morbidities in OSAS. IH can activate several global signaling pathways and various transcription factors such as nuclear factor κB and hypoxia-inducible factor 1α, which play a key role in mediating the inflammatory and cardiovascular consequences in OSAS. This chapter summarized the current literature and our own data on phenotype, functional changes, and inflammatory responses of various blood cells exposed to IH in vivo and in vitro. We focus on the causal relationships between IH and atherogenic transformation of monocytes, lymphocytes, and neutrophils in OSAS patients and on the molecular mechanisms of the cell dysfunctions developed under IH conditions.