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Updated: Apr 30, 2026
Light-sheet Fluorescence Microscopy for the Study of the Murine Heart
Published on: September 15, 2018
The day/night proteome in the murine heart
Insights
The diurnal cardiac proteome varies significantly across the day, impacting cardiovascular function. Disrupting circadian rhythms or the cardiomyocyte clock alters heart protein profiles and function, revealing a role for circadian biology in heart health.
Area of Science:
- Cardiovascular Biology
- Chronobiology
- Proteomics
Background:
- Circadian rhythms are crucial for cardiovascular health and disease.
- Previous studies focused on physiological and gene expression, overlooking protein-level dynamics.
- Understanding the cardiac proteome's daily variation is key to comprehending heart function.
Purpose of the Study:
- To map the 24-hour diurnal cardiac proteome in mice.
- To investigate the impact of circadian disruption on cardiac protein profiles and function.
- To elucidate the role of the cardiomyocyte circadian clock in cardiac metabolism and disease.
Main Methods:
- Two-dimensional difference in-gel electrophoresis (2D-DIGE) and liquid chromatography-mass spectrometry.
- Analysis of diurnal protein variations across the light-dark cycle.
- Utilized cardiomyocyte clock mutant (CCM) mice and a pressure overload cardiac hypertrophy model.
Main Results:
- Approximately 7.8% of the cardiac proteome exhibited significant daily variation.
- Disruption of the light-dark cycle altered cardiac protein profiles and diurnal function.
- CCM hearts showed altered metabolic enzyme expression and loss of time-of-day-dependent ATP consumption.
Conclusions:
- Time of day directly influences cardiac protein abundance.
- Circadian biology offers novel mechanisms contributing to cardiovascular structure and function.
- Circadian clock disruption significantly impacts cardiac proteome and function, particularly in disease states.
Abstract:
Circadian rhythms are essential to cardiovascular health and disease. Temporal coordination of cardiac structure and function has focused primarily at the physiological and gene expression levels, but these analyses are invariably incomplete, not the least because proteins underlie many biological processes. The purpose of this study was to reveal the diurnal cardiac proteome and important contributions to cardiac function. The 24-h day-night murine cardiac proteome was assessed by two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography-mass spectrometry. Daily variation was considerable, as ∼7.8% (90/1,147) of spots exhibited statistical changes at paired times across the 24-h light- (L) dark (D) cycle. JTK_CYCLE was used to investigate underlying diurnal rhythms in corresponding mRNA. We next revealed that disruption of the L:D cycle altered protein profiles and diurnal variation in cardiac function in Langendorff-perfused hearts, relative to the L:D cycle. To investigate the role of the circadian clock mechanism, we used cardiomyocyte clock mutant (CCM) mice. CCM myofilaments exhibited a loss of time-of-day-dependent maximal calcium-dependent ATP consumption, and altered phosphorylation rhythms. Moreover, the cardiac proteome was significantly altered in CCM hearts, especially enzymes regulating vital metabolic pathways. Lastly, we used a model of pressure overload cardiac hypertrophy to demonstrate the temporal proteome during heart disease. Our studies demonstrate that time of day plays a direct role in cardiac protein abundance and indicate a novel mechanistic contribution of circadian biology to cardiovascular structure and function.
