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Series GSE10045 Query DataSets for GSE10045
Status Public on Jan 01, 2008
Title Disruption of the Circadian Clock within the Cardiomyocyte
Organism Mus musculus
Experiment type Expression profiling by array
Summary Disruption of the Circadian Clock within the Cardiomyocyte Influences Myocardial Contractie Function, Metabolism, and Gene Expression
Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally-based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variations in myocardial biology. We therefore generated a cardiomyocyte-specific circadian clock mutant (CCM) mouse, in order to test this hypothesis. At 12 weeks of age, CCM mice exhibit normal myocardial contractile function in vivo, as assessed by echocardiography. Radiotelemetry studies reveal attenuation of heart rate diurnal variations and bradycardia in CCM mice (in the absence of conduction system abnormalities). Reduced heart rate persisted in CCM hearts perfused ex vivo in the working mode, highlighting the intrinsic nature of this phenotype. Wild-type, but not CCM, hearts exhibited a marked diurnal variation in responsiveness to an elevation in workload (80mmHg plus 1 microM epinephrine) ex vivo, with a greater increase in cardiac power and efficiency during the dark (active) phase versus the light (inactive) phase. Moreover, myocardial oxygen consumption and fatty acid oxidation rates were increased, while cardiac efficiency was decreased, in CCM hearts. These observations were associated with no alterations in mitochondrial content or structure, and modest mitochondrial dysfunction, in CCM hearts. Gene expression microarray analysis identified 548 and 176 genes in atria and ventricles, respectively, whose normal diurnal expression patterns were altered in CCM mice. These studies suggest that the cardiomyocyte circadian clock influences myocardial contractile function, metabolism, and gene expression.
Keywords: Comparison of circadian oscillations in gene expression in hearts taken from wildtype and transgenic animals
 
Overall design Atrial and ventricular tissue samples were collected from wildtype and transgenic animals lacking a functional circadian clock within the cardiomyocytes every three hours for a period of 24 hours (n=4 samples per time point; total of 128 samples). Circadian patterns of gene expression were fit for each gene in wild-type atria and ventricle, and then differences in oscillating genes between wild-type and transgenic tissues were determined.
 
Contributor(s) Bray MS, Shaw CA, Moore MW, Garcia RA, Zanquetta MM, Durgan DJ, Jeong WJ, Tsai J, Bugger H, Zhang D, Rohrwasser A, Rennison JH, Dyck JR, Litwin SE, Hardin PE, Chow C, Chandler MP, Abel ED, Young ME
Citation(s) 18156197
Submission date Dec 31, 2007
Last update date Apr 19, 2012
Contact name Molly Bray
E-mail(s) mbray@bcm.edu
Phone 713-798-9311
Fax 713-798-7187
Organization name Baylor College of Medicine
Department Pediatrics/USDA/ARS Children's Nutrition Research Ctr
Street address 1100 Bates, Suite 8070
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
 
Platforms (1)
GPL6333 Illumina Mouse Ref-6 V1
Samples (130)
GSM253799 Atrium Animal 206 zeitgeber time 0 Transgenic
GSM253800 Atrium Animal 276 zeitgeber time 0 Transgenic
GSM253801 Atrium Animal 277 zeitgeber time 0 Transgenic
Relations
BioProject PRJNA108617

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE10045_Bray_CCM_SupplementalData_GEO_122807.xls 423.2 Mb (ftp)(http) XLS
Processed data included within Sample table
Processed data are available on Series record
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