Sleep-disordered breathing and cerebrovascular disease: a mechanistic approach.
The observations described in this article point to the existence of increased oxidative stress and systemic inflammation in sleep apnea and have paved the way for establishing sleep apnea as an independent risk factor for cardio- and cerebrovascular morbidities. The proposed course of events is summarized in Fig. 1. It is suggested that hypoxia/reoxygenation,characteristic of sleep apnea, promotes the formation of ROS, particularly during the reoxygenation period, and can be deleterious to cells and tissues. ROS, however, regulate the activation of critical transcription factors that are redox sensitive, resulting in increased expression of sets of genes that encode proteins essential to adaptation to hypoxia (via hypoxia inducible factor I [hypoxia inducible factor-la]). Yet, redox-sensitive transcription factors (NFKB and AP-1) that elicit inflammatory pathways also are activated, thereby affecting inflammatory and immune responses by promoting activation of endothelial cells, leukocytes, and platelets. These activated cells express adhesion molecules and proinflammatory cytokines that may lead to endothelial injury and dysfunction and consequently to the development of cardio- and cerebrovascular morbidities. These may be exaggerated in patients who have sleep apnea in response to the intermittent hypoxia.
Lavie
Lena
L
The Lloyd Rigler Sleep Apnea Research Laboratory, Unit of Anatomy and Cell Biology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, POB 9649, 31096, Haifa, Israel. lenal@tx.technion.ac.il
D002097:C-Reactive Protein / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000453:epidemiology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012891:Sleep Apnea Syndromes / Q000453:epidemiology* / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000453:epidemiology / Q000378:metabolism; D020521:Stroke / Q000453:epidemiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein