Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression.

Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression. Research Abstract Details 

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Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression. Abstract Text:

Molly S Bray,Chad A Shaw,Michael W S Moore,Rodrigo A P Garcia,Melissa M Zanquetta,David J Durgan,William J Jeong,Ju-Yun Tsai,Heiko Bugger,Dongfang Zhang,Andreas Rohrwasser,Julie H Rennison,Jason R B Dyck,Sheldon E Litwin,Paul E Hardin,Chi-Wing Chow,Margaret P Chandler,E Dale Abel,Martin E Young,Molly S Bray,Chad A Shaw,Michael W S Moore,Rodrigo A P Garcia,Melissa M Zanquetta,David J Durgan,William J Jeong,Ju-Yun Tsai,Heiko Bugger,Dongfang Zhang,Andreas Rohrwasser,Julie H Rennison,Jason R B Dyck,Sheldon E Litwin,Paul E Hardin,Chi-Wing Chow,Margaret P Chandler,E Dale Abel,Martin E Young,

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 to test this hypothesis. At 12 wk 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 (80 mmHg plus 1 muM epinephrine) ex vivo, with a greater increase in cardiac power and efficiency during the dark (active) phase vs. the light (inactive) phase. Moreover, myocardial oxygen consumption and fatty acid oxidation rates were increased, whereas 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.

Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression. Publishing Authors By Initials

MS Bray,CA Shaw,MW Moore,RA Garcia,MM Zanquetta,DJ Durgan,WJ Jeong,JY Tsai,H Bugger,D Zhang,A Rohrwasser,JH Rennison,JR Dyck,SE Litwin,PE Hardin,CW Chow,MP Chandler,ED Abel,ME Young,MS Bray,CA Shaw,MW Moore,RA Garcia,MM Zanquetta,DJ Durgan,WJ Jeong,JY Tsai,H Bugger,D Zhang,A Rohrwasser,JH Rennison,JR Dyck,SE Litwin,PE Hardin,CW Chow,MP Chandler,ED Abel,ME Young,

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Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: American journal of physiology. Heart and circulat

VOLUME: 294

Page Numbers: H1036-47

Journal Abbreviation: Am. J. Physiol. Heart Circ. Ph

ISSN: 0363-6135

DAY: 21

MONTH: 12

YEAR: 2007

Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression.

AFFILIATION: USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Dept. of Pediatrics, 1100 Bates St., Houston, TX 77030. meyoung@bcm.edu).

Country: United States

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MEDLINETA: Am J Physiol Heart Circ Physio

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