ArticleHeart rhythm2015
The cardiomyocyte molecular clock regulates the circadian expression of Kcnh2 and contributes to ventricular repolarization.
Article in Heart rhythm, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Circadian rhythm disruption in cardiovascular disease: a systematic review and meta-analysis of mechanistic evidence from animal models.BMC medicine · 2026Pooled it
- Circadian mechanisms in heart failure: Cell-specific regulation and chrono-medicine.Cell insight · 2026Review
- BMAL1 in cardiovascular diseases: Molecular mechanisms, circadian regulation and translational perspectives (Review).Molecular medicine reports · 2026Review
- Timing of food intake impacts cardiovascular and neuroendocrine physiology and risk of disease.Cardiovascular research · 2026Review
- Circadian clock and its potential as a therapy for ischemic heart disease.Cell communication and signaling : CCS · 2026Review
- Unlocking the potential of circadian biology for cardiovascular health.Physiological reviews · 2026Review
- ANGPTL2 and CP define complementary circadian-associated signals in atrial fibrillation: integrative transcriptomics and external validation.Frontiers in cell and developmental biology · 2026Article
- Review
- Twenty-Four Hour Rhythms in Cardiovascular Physiology.Acta physiologica (Oxford, England) · 2025Review
- Circadian rhythms in cardiovascular disease.European heart journal · 2025Review
- Heart Failure and Arrhythmias: Circadian and Epigenetic Interplay in Myocardial Electrophysiology.International journal of molecular sciences · 2025Review
- Circadian influences on sudden cardiac death and cardiac electrophysiology.Journal of molecular and cellular cardiology · 2025Review
- Morning physical activity may be more beneficial for blood lipids than afternoon physical activity in older adults: a cross-sectional study.European journal of applied physiology · 2024Article
- Feeding behavior modifies the circadian variation in RR and QT intervals by distinct mechanisms in mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2024Article
- Cardiac GR Mediates the Diurnal Rhythm in Ventricular Arrhythmia Susceptibility.Circulation research · 2024Article
- Research progress of circadian rhythm in cardiovascular disease: A bibliometric study from 2002 to 2022.Heliyon · 2024Review
- Circadian Regulation of Cardiac Arrhythmias and Electrophysiology.Circulation research · 2024Review
- The Cardiac Circadian Clock: Implications for Cardiovascular Disease and its Treatment.JACC. Basic to translational science · 2023Review
- Circadian Rhythms in Cardiovascular Function: Implications for Cardiac Diseases and Therapeutic Opportunities.Medical science monitor : international medical journal of experimental and clinical research · 2023Review
- Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology.JACC. Basic to translational science · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSudden cardiac death (SCD) follows a diurnal variation. Data suggest the timing of SCD is influenced by circadian (~24-hour) changes in neurohumoral and cardiomyocyte-specific regulation of the heart's electrical properties. The basic helix-loop-helix transcription factors brain muscle arnt-like1 (BMAL1) and circadian locomotor output control kaput (CLOCK) coordinate the circadian expression of select genes.
objectiveWe sought to test whether Bmal1 expression in cardiomyocytes contributes to K(+) channel expression and diurnal changes in ventricular repolarization.
methodsWe used transgenic mice that allow for the inducible cardiomyocyte-specific deletion of Bmal1 (iCSΔBmal1(-/-)). We used quantitative polymerase chain reaction, voltage clamping, promoter-reporter bioluminescence assays, and electrocardiographic telemetry.
resultsAlthough several K(+) channel gene transcripts were downregulated in iCSΔBmal1(-/-)mouse hearts, only Kcnh2 exhibited a robust circadian pattern of expression that was disrupted in iCSΔBmal1(-/-) hearts. Kcnh2 underlies the rapidly activating delayed-rectifier K(+) current, and the rapidly activating delayed-rectifier K(+) current recorded from iCSΔBmal1(-/-) ventricular cardiomyocytes was ~50% smaller than control ventricular myocytes. Promoter-reporter assays demonstrated that the human Kcnh2 promoter is transactivated by the coexpression of BMAL1 and CLOCK. Electrocardiographic analysis showed that iCSΔBmal1(-/-) mice developed a prolongation in the heart rate-corrected QT interval during the light (resting) phase. This was secondary to an augmented circadian rhythm in the uncorrected QT interval without a corresponding change in the RR interval.
conclusionThe molecular clock in the heart regulates the circadian expression of Kcnh2, modifies K(+) channel gene expression, and is important for normal ventricular repolarization. Disruption of the cardiomyocyte circadian clock mechanism likely unmasks diurnal changes in ventricular repolarization that could contribute to an increased risk of cardiac arrhythmias/SCD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.