Peripheral Endothelial Function, Shift Work, and Circadian Rhythm Disturbances

Suessenbacher et al reported a reduced peripheral arterial tone in shift workers (SW) compared with nonshift workers (NSW), and this endothelial dysfunction could explain, at least in part, the increased cardiovascular risk in SW. We would like to emphasize the possible pivotal role played by circadian rhythm disturbances. Previous studies reported the existence of a circadian variation in basal vascular tone, due at least in part to increased alpha-sympathetic vasoconstrictor activity, and a morning increase of ischemia-induced coronary vascular resistance, that could contribute to the higher incidence of acute cardiac ischemic events at this time. Morning hours, in fact, represent a highest risk period for the onset of various cardiovascular events, such as myocardial infarction, sudden cardiac death, stroke, aortic aneurysm rupture or dissection. Classically, such pattern has been explained with fluctuations in extracardiac factors, i.e., sympathetic activity, vascular tone, sheer stress, prothrombotic factors, but a recent intriguing line of research is focuse to the possibility that a molecular mechanism intrinsic to the cardiomyocite, such as the circadian clock, may contribute to cardiovascular disease. Circadian clocks can be defined as a transcriptionally based molecular mechanism, composed of both positive and negative feedback loops, with a free-running period of approximately 24 hours. The principal circadian clock or master clock, located in the suprachiasmatic nucleus (SCN), is entrained by light and is supposed to entrain peripheral clocks via neurohumoral modulation. Circadian clocks have been identified within almost all mammalian cell types, including cardiomyocytes, vascular smooth muscle cells, and endothelial cells, and circadian clock genes are essential for cardiovascular health. In fact, bmal1 knockout mice or clock mutant mice exhibited impairment of normal protective endothelial responses to vascular injury with intensified pathological remodelling and predisposition to vascular thrombosis. Anticipation is the principal role of cellular biological clocks, since the capacity to know the time of day represents critical information and selective advantage. In fact, such capacity enables organisms to anticipate daily environmental changes and temporally modify behavioural and physiological functions appropriately, and disruption of such rhythms may lead also to negative consequences. It is possible that a dyssynchronization between different cell types (eg, cardiomyocytes, endothelial cells) could contribute to the pathogenesis of cardiovascular diseases, exacerbating preexisting or underlying cardiovascular conditions. Mice exposed to a disrupting 20-hour instead of 24-hour circadian rhythm showed a complete disruption of their sleep/wake behavior and a marked progression of their cardiovascular disease, eg, myocyte hypertrophy and fibrosis. Since the SNC central clock is entrained by light, it is possible that alterations in light/dark cycle conditions, may have consequences on biological clocks, both central and peripheral. The changes in human daily patterns, secondary to the availability of artificial light, and related possible disruption of circadian rhythms (and sleep/wake patterns), may be responsible of cardiovascular disease onset or progression in SW. The results of this study by Dr Suessenbacher et al deserve high consideration. It is possible that SW/NSW activity should be considered when designing or interpreting studies on cardiovascular risk. At now, we have not conclusive data on whether which amount of circadian rhythm disruption or sleep deprivation may be harmful for cardiovascular system. However, we can agree with the statement that harmony between our biology and our environment is vital to good health.