Obstructive sleep apnoea syndrome--an oxidative stress disorder.
Obstructive sleep apnoea syndrome (OSA) is associated with increased cardiovascular morbidity and mortality. However, the underlying mechanisms are not entirely understood. This review will summarize the evidence that substantiates the notion that the repeated apnoea-related hypoxic events in OSA, similarly to hypoxia/reperfusion injury, initiate oxidative stress. Thus, affecting energy metabolism, redox-sensitive gene expression, and expression of adhesion molecules. A limited number of studies substantiate this hypothesis directly by demonstrating increased free radical production in OSA leukocytes and increased plasma-lipid peroxidation. A great number of studies, however, support this hypothesis indirectly. Increase in circulating levels of adenosine and urinary uric acid in OSA are implicated with increased production of reactive oxygen species (ROS). Activation of redox-sensitive gene expression is suggested by the increase in some protein products of these genes, including VEGF, erythropoietin, endothelin-1, inflammatory cytokines and adhesion molecules. These implicate the participation of redox-sensitive transcription factors as HIF-1 AP-1 and NFkappaB. Finally, adhesion molecule-dependent increased avidity of OSA monocytes to endothelial cells, combined with diminished NO bioavailability, lead to exaggerated endothelial cell damage and dysfunction. Cumulatively, these processes may exacerbate atherogenic sequelae in OSA.
Lavie
Lena
L
Anatomy and Cell Biology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. lenal@techunix.technion.ac.il
D002318:Cardiovascular Diseases / Q000209:etiology; D016228:Endothelial Growth Factors / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008222:Lymphokines / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D005609:Free Radicals; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide