Watching the clock: Blood pressure and cardiovascular disease influence circadian machinery in pre-clinical models.

Abstract

Circadian rhythms drive cardiovascular health, and when dysfunctional, disease. Circadian biology rules daily rhythms in physiological mechanisms which allow our bodies to coordinate function with the demands of the external environment. However, the machinery underlying circadian rhythms, termed the "molecular clock", can become altered by both external and internal factors. For instance, breaking the clock through disrupted light exposure can drive high blood pressure, which is detrimental to cardiovascular health. Importantly, cardiovascular disease itself can disrupt the molecular clock, further exacerbating pathology. The focus of this review is this latter aspect of the bi-directional relationship between circadian machinery and cardiovascular function, investigated in preclinical models. First, we describe the importance of blood pressure regulation and relevant systems. We then describe the existence of circadian rhythms in blood pressure, and briefly, how a broken clock can disrupt these rhythms and lead to disease. The focus of this review will be to outline evidence from pre-clinical and translational studies investigating the direct impact of cardiovascular disease on circadian machinery in the brain, heart, aorta, and kidney. This is with the goal of 1) highlighting the potential for harnessing the molecular clock through circadian interventions in combination with other treatment, and 2) aiding pre-clinical cardiovascular researchers in understanding their results which may be impacted by time of day.