1. Academic Validation
  2. Light-induced circadian rhythm disorder leads to microvascular dysfunction via up-regulating NETs

Light-induced circadian rhythm disorder leads to microvascular dysfunction via up-regulating NETs

  • Microvasc Res. 2023 Aug 9;104592. doi: 10.1016/j.mvr.2023.104592.
Zhanhui Wang 1 Fupeng Yang 2 Zhiqing He 3 Chun Liang 4
Affiliations

Affiliations

  • 1 Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai, China; Department of Health Care Section, 971th Hospital of PLA, Qingdao, China.
  • 2 Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai, China.
  • 3 Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai, China. Electronic address: dragonhzq@yeah.net.
  • 4 Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai, China. Electronic address: chunliangliang1985@163.com.
Abstract

Circadian rhythm is a physical, mental, and behavioral pattern over the course of 24-hour cycle, and its disturbance is associated with increased risk of cardiovascular diseases. Microvascular dysfunction serves as an important cause of Cardiovascular Disease, but the relationship between rhythm disturbances and microcirculation remains elusive. Herein, we constructed the mice model of circadian rhythm disturbance and investigated the alterations of microvascular conditions. It was revealed that coronary microcirculatory function and cardiac diastolic function were significantly reduced, along with endothelium-dependent diastolic function of microvessels remarkably impaired in the rhythm-disordered group of mice compared to the control group. Notably, rhythm disturbance led to a significant upregulation of neutrophil extracellular traps (NETs) levels in mice, which cause endothelial dysfunction by inhibiting microvascular endothelial cell activity and migration capacity as well as inducing Apoptosis. Additionally, intraperitoneal injection of Cl-amidine suppressed the production of NETs, which further improved coronary microcirculatory function and endothelium-dependent diastolic function. In conclusion, this study demonstrated that circadian rhythm disorders could induce the development of coronary microvascular dysfunction (CMD) through the up-regulation of NETs, providing a potential therapeutic direction for the treatment of CMD.

Keywords

Circadian rhythm disorders; Endothelial dysfunction; Microvascular dysfunction; Neutrophil extracellular traps.

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