Intermittent hypoxia: the culprit of oxidative stress, vascular inflammation and dyslipidemia in obstructive sleep apnea.

Obstructive sleep apnea, a breathing disorder in sleep characterized by intermittent and recurrent pauses in respiration, is also a major risk factor for cardiovascular morbidity and mortality. Accumulated evidence implicates the apnea-related multiple cycles of hypoxia/reoxygenation in promoting the formation of reactive oxygen species that oxidize and damage macromolecules and activate critical redox-sensitive signaling pathways and transcription factors. This activation facilitates the expression of sets of genes encoding proteins in various pathways, including inflammatory and lipogenic, as well as proteins essential to adaptation to hypoxia. Consequently, inflammatory and immune responses are activated, thus resulting in the activation of endothelial cells/leukocytes/platelets. These activated cells express adhesion molecules and proinflammatory cytokines that in turn may further exacerbate inflammatory responses and cause endothelial cell injury and dysfunction, promoting the development of cardiovascular morbidities in sleep apnea. No less important in activating such inflammatory cascades is the hyperlipidemia that is another characteristic of obstructive sleep apnea. Evidence supporting the existence of endothelial dysfunction and early clinical signs of atherosclerosis in these patients provides a firm support to the above chain of events. If left untreated, this cascade of events may eventually lead to overt cardiovascular morbidity.