Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai, China; Department of Health Care Section, 971th Hospital of PLA, Qingdao, China.
Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai, China.
Microvasc Res. 2023 Nov;150:104592. doi: 10.1016/j.mvr.2023.104592. Epub 2023 Aug 9.
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.
昼夜节律是 24 小时周期内的生理、心理和行为模式，其紊乱与心血管疾病风险增加有关。微血管功能障碍是心血管疾病的重要原因，但节律紊乱与微循环之间的关系仍不清楚。在此，我们构建了昼夜节律紊乱的小鼠模型，并研究了其微血管状态的变化。结果显示，与对照组相比，节律紊乱组小鼠的冠状动脉微循环功能和心脏舒张功能明显降低，微血管内皮依赖性舒张功能显著受损。值得注意的是，节律紊乱导致小鼠中性粒细胞胞外诱捕网（NETs）水平显著上调，通过抑制微血管内皮细胞的活性和迁移能力以及诱导细胞凋亡导致内皮功能障碍。此外，腹腔注射 Cl-amidine 可抑制 NETs 的产生，进一步改善冠状动脉微循环功能和内皮依赖性舒张功能。总之，本研究表明，昼夜节律紊乱可通过上调 NETs 诱导冠状动脉微血管功能障碍（CMD）的发生，为 CMD 的治疗提供了一个潜在的治疗方向。
