Chronobiological Influence Over Cardiovascular Function: The Good, the Bad, and the Ugly

Overview

Journal Circ Res

Specialty Cardiology & Vascular Diseases

Date 2020 Jan 17

PMID 31944922

Citations 44

Authors

Samir Rana

Sumanth D Prabhu

Martin E Young

Affiliations

Soon will be listed here.

Abstract

Essentially all biological processes fluctuate over the course of the day, observed at cellular (eg, transcription, translation, and signaling), organ (eg, contractility and metabolism), and whole-body (eg, physical activity and appetite) levels. It is, therefore, not surprising that both cardiovascular physiology (eg, heart rate and blood pressure) and pathophysiology (eg, onset of adverse cardiovascular events) oscillate during the 24-hour day. Chronobiological influence over biological processes involves a complex interaction of factors that are extrinsic (eg, neurohumoral factors) and intrinsic (eg, circadian clocks) to cells. Here, we focus on circadian governance of 6 fundamentally important processes: metabolism, signaling, electrophysiology, extracellular matrix, clotting, and inflammation. In each case, we discuss (1) the physiological significance for circadian regulation of these processes (ie, the good); (2) the pathological consequence of circadian governance impairment (ie, the bad); and (3) whether persistence/augmentation of circadian influences contribute to pathogenesis during distinct disease states (ie, the ugly). Finally, the translational impact of chronobiology on cardiovascular disease is highlighted.

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References

Schoenhard J, Smith L, Painter C, Eren M, Johnson C, Vaughan D . Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2. J Mol Cell Cardiol. 2003; 35(5):473-81. DOI: 10.1016/s0022-2828(03)00051-8. View

Malik M, Farrell T, Camm A . Circadian rhythm of heart rate variability after acute myocardial infarction and its influence on the prognostic value of heart rate variability. Am J Cardiol. 1990; 66(15):1049-54. DOI: 10.1016/0002-9149(90)90503-s. View

Narasimamurthy R, Hatori M, Nayak S, Liu F, Panda S, Verma I . Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines. Proc Natl Acad Sci U S A. 2012; 109(31):12662-7. PMC: 3411996. DOI: 10.1073/pnas.1209965109. View

Shang X, Pati P, Anea C, Fulton D, Rudic R . Differential Regulation of BMAL1, CLOCK, and Endothelial Signaling in the Aortic Arch and Ligated Common Carotid Artery. J Vasc Res. 2016; 53(5-6):269-278. PMC: 5765856. DOI: 10.1159/000452410. View

Carter S, Durrington H, Gibbs J, Blaikley J, Loudon A, Ray D . A matter of time: study of circadian clocks and their role in inflammation. J Leukoc Biol. 2016; 99(4):549-60. DOI: 10.1189/jlb.3RU1015-451R. View

Silver A, Arjona A, Walker W, Fikrig E . The circadian clock controls toll-like receptor 9-mediated innate and adaptive immunity. Immunity. 2012; 36(2):251-61. PMC: 3315694. DOI: 10.1016/j.immuni.2011.12.017. View

Reinberg A, GHATA J, Halberg F, Gervais P, Abulker C, Dupont J . [Circadian rhythm of pulse, arterial blood pressure, urinary excretions of 17-hydroxycorticosteroids catecholamines and potassium in healthy adult humans active and during rest]. Ann Endocrinol (Paris). 1970; 31(2):277-87. View

Takahashi J, Hong H, Ko C, McDearmon E . The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev Genet. 2008; 9(10):764-75. PMC: 3758473. DOI: 10.1038/nrg2430. View

Nelson W, KUPFERBERG H, Halberg F . Dose-response evaluations of a circadian rhythmic change in susceptibility of mice to ouabain. Toxicol Appl Pharmacol. 1971; 18(2):335-9. DOI: 10.1016/0041-008x(71)90125-6. View

10.

Couch R . Travel, time zones, and sudden cardiac death. Emporiatric pathology. Am J Forensic Med Pathol. 1990; 11(2):106-11. DOI: 10.1097/00000433-199006000-00003. View

11.

Vyas M, Garg A, Iansavichus A, Costella J, Donner A, Laugsand L . Shift work and vascular events: systematic review and meta-analysis. BMJ. 2012; 345:e4800. PMC: 3406223. DOI: 10.1136/bmj.e4800. View

12.

Schroder E, Lefta M, Zhang X, Bartos D, Feng H, Zhao Y . The cardiomyocyte molecular clock, regulation of Scn5a, and arrhythmia susceptibility. Am J Physiol Cell Physiol. 2013; 304(10):C954-65. PMC: 3651636. DOI: 10.1152/ajpcell.00383.2012. View

13.

Curtis A, Bellet M, Sassone-Corsi P, ONeill L . Circadian clock proteins and immunity. Immunity. 2014; 40(2):178-86. DOI: 10.1016/j.immuni.2014.02.002. View

14.

Castanon-Cervantes O, Wu M, Ehlen J, Paul K, Gamble K, Johnson R . Dysregulation of inflammatory responses by chronic circadian disruption. J Immunol. 2010; 185(10):5796-805. PMC: 2974025. DOI: 10.4049/jimmunol.1001026. View

15.

Verdecchia P, Schillaci G, Guerrieri M, GATTESCHI C, Benemio G, Boldrini F . Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation. 1990; 81(2):528-36. DOI: 10.1161/01.cir.81.2.528. View

16.

Muntner P, Lewis C, Diaz K, Carson A, Kim Y, Calhoun D . Racial differences in abnormal ambulatory blood pressure monitoring measures: Results from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Am J Hypertens. 2014; 28(5):640-8. PMC: 4415060. DOI: 10.1093/ajh/hpu193. View

17.

Pekovic-Vaughan V, Gibbs J, Yoshitane H, Yang N, Pathiranage D, Guo B . The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis. Genes Dev. 2014; 28(6):548-60. PMC: 3967045. DOI: 10.1101/gad.237081.113. View

18.

Bass J, Takahashi J . Circadian integration of metabolism and energetics. Science. 2010; 330(6009):1349-54. PMC: 3756146. DOI: 10.1126/science.1195027. View

19.

Jeyaraj D, Haldar S, Wan X, McCauley M, Ripperger J, Hu K . Circadian rhythms govern cardiac repolarization and arrhythmogenesis. Nature. 2012; 483(7387):96-9. PMC: 3297978. DOI: 10.1038/nature10852. View

20.

Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U . The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell. 2002; 110(2):251-60. DOI: 10.1016/s0092-8674(02)00825-5. View