昼夜节律
内科学
内皮
微循环
节奏
内皮功能障碍
医学
心脏病学
下调和上调
内分泌学
舒张期
生物
血压
生物化学
基因
作者
Zhanhui Wang,Fengling Yang,Zhiqing He,Chun Liang
标识
DOI:10.1016/j.mvr.2023.104592
摘要
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.
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