Published Online
on October 17, 2005

A more recent version of this article appeared on October 25, 2005

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Submitted on February 9, 2005
Revised on August 1, 2005
Accepted on August 3, 2005

Bioinformatic Analysis of Circadian Gene Oscillation in Mouse Aorta

R. Daniel Rudic PhD, Peter McNamara PhD, Dermot Reilly PhD, Tilo Grosser MD, Anne-Marie Curtis BS, Thomas S. Price PhD, Satchidananda Panda PhD, John B. Hogenesch PhD, and Garret A. FitzGerald MD^*

From the Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia (R.D.R., D.R., T.G., A.-M.C., T.S.P., G.A.F.); the Phenomix Corporation, La Jolla, Calif (P.M.); the Salk Institute for Biological Studies, La Jolla, Calif (S.P.); and Scripps Florida, Jupiter, Fla (J.B.H.).

^* To whom correspondence should be addressed. E-mail: garret{at}spirit.gcrc.upenn.edu.

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.

Key words: aorta • circadian rhythm • metabolism • vasculature • genes

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