Description
The National Heart, Lung, and Blood Institute in partnership with the National Institute on Aging, and the National Cancer Institute convened a Working Group to discuss circadian-coupled function in peripheral cardiovascular, metabolic, lung, and hematopoient tissues on September 20, 2007, in Baltimore, Maryland. The panel included investigators with expertise ranging from epidemiology to genetics, genomics, physiology, and cell biology. The working group assessed the role of circadian-coupled dysregulation in peripheral tissue pathophysiology, and the importance of clock-related proteins as “sensors” that translates chemical signals from the cellular environment into specific genomic responses within peripheral organs such as heart, lung, blood, vasculature, liver, pancreas, fat, and muscle.
At an organismal level, circadian-related proteins are critical to most forms of life. The circadian genes are highly conserved evolutionarily and their expression ubiquitous. Several lines of emerging evidence link circadian-coupled proteins to both the temporal organization of cellular function, and to inducible transcriptional networks responsive to stimuli such as hypoxia, light, temperature, nutrients, catecholamines, anabolic hormones, and toxic molecules. Recent studies in which circadian transcription networks were disrupted at the genomic, proteomic, cellular or physiological levels implicate abnormalities in circadian-coupled cellular function with myocardial infarction, arrhythmogenicity, hypoxic injury, congestive heart failure, skeletal muscle weakness, coagulopathy, metabolic syndrome, glucose and lipid dysregulation. These findings suggest that recent advances in understanding circadian-coupled function in peripheral tissues have significant implications for our understanding of cardiovascular and metabolic homeostasis, and whether environmental or genetic disruption of these cell autonomous molecular mechanisms contribute to the development of cardiometabolic syndrome and disorders of the lung and blood.