Bioinformatic Analysis of Circadian Gene Oscillation in Mouse Aorta

Abstract

Background— Circadian rhythmicity of many aspects of cardiovascular function—blood pressure, coagulation and contractile function—is well established, as is diurnal variation in important clinical events, such as myocardial infarction and stroke. Here, we undertake studies to globally assess circadian gene expression in murine aorta. Methods and Results— Aortae from mice were harvested at 4-hour intervals for 2 circadian cycles (48 hours). Gene expression was assessed by expression profiling and subjected to a gene ontology bioinformatics analysis. Three hundred thirty transcripts exhibited a circadian pattern of oscillation in mouse aorta, including those intrinsic to the function of the molecular clock. In addition, many genes relevant to protein folding, protein degradation, glucose and lipid metabolism, adipocyte maturation, vascular integrity, and the response to injury are also included in this subset of roughly 7000 genes screened for circadian oscillation. Conclusions— Detection of functional cassettes of vascular genes that exhibit circadian regulation in the mouse will facilitate elucidation of the mechanisms by which the molecular clock may interact with environmental variables to modulate cardiovascular function and the response to therapeutic interventions.

Genetic Components of the Circadian Clock Regulate Thrombogenesis In Vivo

“…16 Cassettes of genes relevant to vascular injury and integrity have been shown to oscillate in mouse aorta, as does vascular leakage. 2 We have recently implicated the molecular clock in regulating circadian variation in BP and the response to asynchronous stress. 17 The present study sought to determine whether genes that are key components of the molecular clock might also regulate the response to a thrombogenic stimulus in vivo.…”

“…In mammals, the master oscillator is located in the suprachiasmatic nucleus, 1 and autonomous peripheral oscillators have been defined for most tissues, including the vasculature, heart, and kidney. [2][3][4] Peripheral oscillators, which share many of their molecular components with the master oscillator, can also be distinguished by the expression of specific transcription factors (eg, NPAS2 and CLIF in the vasculature). 3,5 The molecular oscillator is composed of interlocking positive and negative transcriptional and translational feedback loops that drive circadian gene expression.…”

Rhythm changes of clock genes, apoptosis-related genes and atherosclerosis-related genes in apolipoprotein E knockout mice

“…M any aspects of cardiovascular function are subject to diurnal variation, although the precise role of the circadian clock in these phenomena remains largely undetermined (1). Acute cardiovascular events exhibit an obvious circadian rhythm in the frequency of occurrence (2).…”

Integration of metabolic and cardiovascular diurnal rhythms by circadian clock

“…Importantly, these rhythms are dampened in heart-specific Clock mutants [44], indicating that the circadian system governs the diurnal rhythms of energy metabolism in the heart. Genome-wide expression analyses using the murine aortic tissue, which revealed that the expression of a large number of metabolic genes important for glucose and lipid metabolism follows a circadian pattern [46], further point to a link between circadian and metabolic functions in cardiovascular tissues.…”