Journal article
Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression
American journal of physiology. Heart and circulatory physiology, Vol.294(2), pp.H1036-1047
02/2008
DOI: 10.1152/ajpheart.01291.2007
PMID: 18156197
Abstract
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 microM 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.
Details
- Title: Subtitle
- Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression
- Creators
- Molly S Bray - US Department of Agriculture, Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Houston, TX 77030, USAChad A ShawMichael W S MooreRodrigo A P GarciaMelissa M ZanquettaDavid J DurganWilliam J JeongJu-Yun TsaiHeiko BuggerDongfang ZhangAndreas RohrwasserJulie H RennisonJason R B DyckSheldon E LitwinPaul E HardinChi-Wing ChowMargaret P ChandlerE Dale AbelMartin E Young
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.294(2), pp.H1036-1047
- Publisher
- United States
- DOI
- 10.1152/ajpheart.01291.2007
- PMID
- 18156197
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Grant note
- HL-074259 / NHLBI NIH HHS HL-070070 / NHLBI NIH HHS
- Language
- English
- Date published
- 02/2008
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024529902771
Metrics
15 Record Views