A Wrinkle in Time: Circadian biology in pulmonary vascular health and disease

An often over looked element of pulmonary vascular disease is time. Cellular responses to time, which are regulated directly by the core circadian clock, have only recently been elucidated. Despite an extensive collection of data regarding the role of rhythmic contribution to disease pathogenesis (such as systemic hypertension, coronary artery and renal disease), the roles of key circadian transcription factors in pulmonary hypertension remain under-studied. This is despite a large degree of overlap in the pulmonary hypertension and circadian rhythm fields, including not only shared signaling pathways, but also cell-specific effects of the core clock that are known to result in both protective and adverse lung vessel changes. Therefore, the goal of this review is to summarize the current dialogue regarding common pathways in circadian biology, with a specific emphasis on its implications in the progression of pulmonary hypertension. In this work, we emphasize specific proteins involved in the regulation of the core molecular clock while noting the circadian cell-specific changes relevant to vascular remodeling. Finally, we apply this knowledge to the optimization of medical therapy, with a focus on sleep hygiene and the role of chronopharmacology in patients with this disease. In dissecting the unique relationship between time and cellular biology, we aim to provide valuable insight into the practical implications of considering time as a therapeutic variable. Armed with this information, physicians will be positioned to more efficiently utilize the full four dimensions of patient care, resulting in improved morbidity and mortality of pulmonary hypertension patients.

Circadian Biology in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a complex process that can lead to the dysregulation of the molecular clock, as well as 24 h rhythms of sleep and wake, blood pressure, and other associated biological processes. Previous work has demonstrated crosstalk between the circadian clock and hypoxia-responsive pathways. However, even in the absence of OSA, disrupted clocks can exacerbate OSA-associated outcomes (e.g., cardiovascular or cognitive outcomes). As we expand our understanding of circadian biology in the setting of OSA, this information could play a significant role in the diagnosis and treatment of OSA. Here, we summarize the pre-existing knowledge of circadian biology in patients with OSA and examine the utility of circadian biomarkers as alternative clinical tools.

Circadian Biology and Stroke

Circadian biology modulates almost all aspects of mammalian physiology, disease, and response to therapies. Emerging data suggest that circadian biology may significantly affect the mechanisms of susceptibility, injury, recovery, and the response to therapy in stroke. In this review/perspective, we survey the accumulating literature and attempt to connect molecular, cellular, and physiological pathways in circadian biology to clinical consequences in stroke. Accounting for the complex and multifactorial effects of circadian rhythm may improve translational opportunities for stroke diagnostics and therapeutics.

Nighttime Light Hurts Mammalian Physiology: What Diurnal Rodent Models Are Telling Us

Natural sunlight permits organisms to synchronize their physiology to the external world. However, in current times, natural sunlight has been replaced by artificial light in both day and nighttime. While in the daytime, indoor artificial light is of lower intensity than natural sunlight, leading to a weak entrainment signal for our internal biological clock, at night the exposure to artificial light perturbs the body clock and sleep. Although electric light at night allows us “to live in darkness”, our current lifestyle facilitates nighttime exposure to light by the use, or abuse, of electronic devices (e.g., smartphones). The chronic exposure to light at nighttime has been correlated to mood alterations, metabolic dysfunctions, and poor cognition. To decipher the brain mechanisms underlying these alterations, fundamental research has been conducted using animal models, principally of nocturnal nature (e.g., mice). Nevertheless, because of the diurnal nature of human physiology, it is also important to find and propose diurnal animal models for the study of the light effects in circadian biology. The present review provides an overview of the effects of light at nighttime on physiology and behavior in diurnal mammals, including humans. Knowing how the brain reacts to artificial light exposure, using diurnal rodent models, is fundamental for the development of new strategies in human health based in circadian biology.

Accounting for Time: Circadian Rhythms in the Time of COVID-19

The COVID-19 pandemic has necessitated novel approaches and collaborative efforts across multiple disciplines. It is known that various aspects of our physiology and response to pathogens are under tight clock control. However, the assimilation of circadian biology into our clinical and research practices is still evolving. Using a focused review of the literature and original analyses of the UK Biobank, we discuss how circadian biology may inform our diagnostic and therapeutic strategies in this pandemic.