Obstructive sleep apnoea: time for a radical change?

R eactive oxygen species (ROS) are highly reactive molecules that originate from both (intra-and extra-cellular) endogenous sources and from exogenous sources. They can be broadly divided into free radicals and nonradical reactive species; STOCKER and KEANEY [1] have examined this in a more extensive review. In the basal state, ROS play an essential physiological role in cellular signalling pathways and transcriptional regulation, which act to maintain cellular homeostasis [2]. In contrast, oxidative stress is characterised by an excess of ROS, which can ultimately result in cellular injury via reactions with proteins, nucleic acids and lipids. As such, oxidative stress is hypothesised to play a primary role in the development of many disease processes, including atherosclerosis. The oxidative modification hypothesis of atherosclerosis centres on the well-known association between low-density lipoprotein (LDL) cholesterol and atherosclerosis and, in particular, on the uptake of oxidised LDL by macrophages within the arterial wall to form foam cells, the earliest stage in atherogenesis. In addition to inflammatory cells, there are a number of vascular cell types, including vascular smooth muscle cells, endothelial cells and adventitial fibroblasts, which all provide a source of oxidants within the vessel wall and could play a role in the conversion of LDL into its oxidised (high-uptake) form. The metabolic and enzymatic sources of ROS include (but are not limited to) nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, nitric oxide synthase, myeloperoxidase, lipoxygenase and mitochon-drial respiration [1, 3]. The intra-and extracellular accumulation of the various forms of ROS are limited by several endogenous and dietary-derived antioxidants. These antioxidant defences act by directly suppressing the generation of free radicals, by scavenging radicals and repairing damaged cells [4]. They can be broadly divided into three types. Enzymatic antioxidants include the superoxide dismutases and peroxidases (e.g. glutathione peroxidase), which act to remove most superoxides and peroxides from within cells. Metal-chelating proteins are antioxidants involved in the sequestration of transition metals (iron and copper) that can induce oxidative damage. Finally, the nonproteinaceous antioxidants include water-soluble (e.g. ascorbate and uric acid) and lipid-soluble (e.g. vitamin E, the tocopherols) forms, of which the latter plays a crucial antioxidant role in radical-induced lipid peroxidation. The potential role of oxidative stress in the aetiopathogenesis of atherosclerosis has been extensively investigated in conditions that predispose to cardiovascular disease. Obstructive sleep apnoea (OSA) is one such condition. In the past decade, numerous studies have increasingly provided evidence linking OSA to the development …