Cardiac circadian rhythms in time and space: The future is in 4D

The circadian clock synchronizes the body into 24-h cycles, thereby anticipating variations in tissue-specific diurnal tasks, such as response to increased cardiac metabolic demand during the active period of the day. As a result, blood pressure, heart rate, cardiac output, and occurrence of fatal cardiovascular events fluctuate in a diurnal manner. The heart contains different cell types that make up and reside in an environment of biochemical, mechanical, and topographical signaling. Cardiac architecture is essential for proper heart development as well as for maintenance of cell homeostasis and tissue repair. In this review, we describe the possibilities of studying circadian rhythmicity in the heart by using advanced in vitro systems that mimic the native cardiac 3D microenvironment which can be tuned in time and space. Harnessing the knowledge that originates from those in vitro models could significantly improve innovative cardiac modeling and regenerative strategies.