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In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
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Light-induced circadian rhythm disorder leads to microvascular dysfunction via up-regulating NETs
Zhanhui Wang1, Fupeng Yang2, Zhiqing He2
1Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai, China; Department of Health Care Section, 971th Hospital of PLA, Qingdao, China.
Microvascular Research
|August 11, 2023
Summary
Circadian rhythm disruption impairs heart microcirculation by increasing neutrophil extracellular traps (NETs). Suppressing NETs with Cl-amidine improved heart function, suggesting a new therapeutic target for cardiovascular disease.
Area of Science:
- Cardiovascular Science
- Chronobiology
- Immunology
Background:
- Circadian rhythm disturbances are linked to cardiovascular disease risk.
- The impact of circadian disruption on microcirculation is not well understood.
- Microvascular dysfunction is a key factor in cardiovascular pathologies.
Purpose of the Study:
- To investigate the effects of circadian rhythm disturbance on coronary microcirculation.
- To elucidate the mechanisms linking circadian disruption to microvascular dysfunction.
- To explore potential therapeutic interventions for rhythm-disruption-induced cardiovascular issues.
Main Methods:
- Established a mouse model of circadian rhythm disturbance.
- Assessed coronary microcirculatory and cardiac diastolic function.
- Quantified neutrophil extracellular traps (NETs) levels.
- Evaluated the impact of Cl-amidine on NETs production and microvascular function.
Main Results:
- Circadian rhythm disorder significantly impaired coronary microcirculation and cardiac diastolic function.
- Endothelium-dependent microvascular diastolic function was notably reduced.
- Neutrophil extracellular traps (NETs) levels were upregulated, causing endothelial dysfunction.
- Cl-amidine treatment reduced NETs and improved microvascular and cardiac function.
Conclusions:
- Circadian rhythm disorders induce coronary microvascular dysfunction (CMD) via NETs upregulation.
- NETs play a critical role in endothelial dysfunction associated with circadian disruption.
- NETs inhibition presents a potential therapeutic strategy for CMD.
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