Title:Circadian-Hypoxia Link and its Potential for Treatment of Cardiovascular Disease
VOLUME: 25 ISSUE: 10
Author(s):Colleen Marie Bartman and Tobias Eckle*
Affiliation:Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, Graduate Training Program in Cell Biology, Stem Cells, and Development, University of Colorado Anschutz Medical Campus, Aurora, CO, Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, Graduate Training Program in Cell Biology, Stem Cells, and Development, University of Colorado Anschutz Medical Campus, Aurora, CO
Keywords:PER2, hypoxia, HIF1, circadian biology, circadian disruption, myocardial ischemia.
Abstract:Throughout the evolutionary time, all organisms and species on Earth evolved with an adaptation to
consistent oscillations of sunlight and darkness, now recognized as ‘circadian rhythm.’ Single-cellular to multisystem
organisms use circadian biology to synchronize to the external environment and provide predictive adaptation
to changes in cellular homeostasis. Dysregulation of circadian biology has been implicated in numerous
prevalent human diseases, and subsequently targeting the circadian machinery may provide innovative preventative
or treatment strategies. Discovery of ‘peripheral circadian clocks’ unleashed widespread investigations into
the potential roles of clock biology in cellular, tissue, and organ function in healthy and diseased states. Particularly,
oxygen-sensing pathways (e.g. hypoxia inducible factor, HIF1), are critical for adaptation to changes in
oxygen availability in diseases such as myocardial ischemia. Recent investigations have identified a connection
between the circadian rhythm protein Period 2 (PER2) and HIF1A that may elucidate an evolutionarily conserved
cellular network that can be targeted to manipulate metabolic function in stressed conditions like hypoxia or
ischemia. Understanding the link between circadian and hypoxia pathways may provide insights and subsequent
innovative therapeutic strategies for patients with myocardial ischemia. This review addresses our current understanding
of the connection between light-sensing pathways (PER2), and oxygen-sensing pathways (HIF1A), in
the context of myocardial ischemia and lays the groundwork for future studies to take advantage of these two
evolutionarily conserved pathways in the treatment of myocardial ischemia.