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(Circulation. 2005;112:2716-2724.)
© 2005 American Heart Association, Inc.

Vascular Medicine

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; 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.).

Correspondence to Garret A. FitzGerald, MD, The Institute for Translational Medicine and Therapeutics, 153 Johnson Pavilion, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104. E-mail garret{at}spirit.gcrc.upenn.edu

Received February 9, 2005; de novo received June 13, 2005; revision received August 1, 2005; accepted August 3, 2005.

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.

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