Are cardiorespiratory complications a question of epigenetics?

T he character Joe from Charles Dickens’ The Posthumous Papers of the Pickwick Club (1837) was markedly obese and often fell asleep in an uncontrollable way during the day (1). This is probably one of thefirst cases of sleep apnea syndrome described in the literature. Sleep apnea is most often due to upper airway obstructions during sleep (2) and is regarded as a national disease affecting approximately 4% of the adult population. It results in intermittent hypoxia, leading to cardiovascular complications such as hypertension, coronary artery disease, heart failure, and stroke (3). The incidence of intermittent hypoxia is also common among infants, particularly if they are born prematurely (4). It increases the risk for developing cerebral palsy and sudden infant death syndrome (SIDS) (5). In PNAS, Nanduri et al. (6) report epigenetic regulation of hypoxic sensing. Neonatal rats from day 1 to day 10 were exposed to intermittent hypoxia in alternating cycles for 15 s of 5% oxygen with air for 5 min, which corresponds fairly well with clinical apnea. When their respiration and other autonomic functions were monitored as adults they showed exaggerated responses to hypoxia by the carotid bodies. Furthermore, the authors found that the adrenal chromaffin cells responded to the hypoxia with enhanced catecholamine secretion. It seems likely that the sympathetic nervous system was also activated, possibly leading to hypertension.