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Published on: August 8, 2019
Abnormal circadian rhythms are associated with plaque instability in acute coronary syndrome patients
Zai-Qiang Zhang1,2, Jia-Wang Ding1,2, Xin-An Wang1,2
1Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University Yichang 443000, Hubei Province, PR China.
Insights
Circadian rhythm disruptions are linked to acute coronary syndrome (ACS) and reduced plaque stability in patients. Lower expression of core clock genes correlates with increased matrix metalloproteinase (MMP) levels, indicating poorer plaque stability in ACS.
Area of Science:
- Cardiovascular Medicine
- Chronobiology
- Molecular Biology
Background:
- Acute coronary syndrome (ACS) is a significant global health concern.
- Circadian rhythms, internal biological clocks, are fundamental to physiological processes.
- The interplay between circadian rhythms and plaque instability in ACS remains poorly understood.
Purpose of the Study:
- To investigate the relationship between circadian rhythm parameters and plaque instability in ACS patients.
- To explore the expression levels of key circadian clock genes and matrix metalloproteinases (MMPs) in ACS.
Main Methods:
- Assessed circadian rhythms using validated questionnaires (AIS, PSQI, IPAQ) and a Healthy Diet Score (HDS).
- Quantified mRNA expression of core clock genes (Bmal1, Clock, Cry1, Per2, Rev-erbα) and MMPs (MMP2, MMP9) via qRT-PCR.
- Compared these markers between ACS patient subgroups (STEMI, NSTEMI, UA) and normal controls (NCs).
Main Results:
- ACS patients exhibited poorer circadian rhythm scores (higher AIS/PSQI) and lower physical activity (IPAQ) compared to controls.
- Expression of clock genes (Bmal1, Clock, Cry1, Per2, Rev-erbα) was significantly reduced in ACS patients.
- MMP2 and MMP9 mRNA levels were elevated in ACS patients, negatively correlating with clock gene expression.
Conclusions:
- Circadian rhythm disturbances are associated with the occurrence of ACS.
- Reduced expression of core clock genes correlates with decreased plaque stability in ACS patients.
- These findings highlight the potential role of circadian clock dysfunction in ACS pathogenesis.
Aim:
Acute coronary syndrome (ACS), a leading cause of morbidity and mortality worldwide, is among the most serious cardiovascular diseases. Circadian rhythms are present in almost all organisms. In clinical practice, we have found that ACS is closely related to these circadian rhythms. However, the relationship between circadian rhythms and plaque instability in ACS patients is incompletely understood. The aim of this study is to provide new insights into the relationship between circadian rhythms and plaque instability in ACS patients.
Methods:
We enrolled patients with ACS and individuals with normal coronary artery function in this study. The Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI), International Physical Activity Questionnaire (IPAQ) and Healthy Diet Score (HDS) were used to evaluate circadian rhythms. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the mRNA expression levels of muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), Cryptochrome1 (Cry1), Period2 (Per2), nuclear receptor subfamily 1, group D, member 1 (Rev-erbα), and matrix metalloproteinases MMP2 and MMP9.
Results:
AIS scores and PSQI scores were significantly higher in patients with ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI), and unstable angina pectoris (UA) than in the normal controls (NCs) (P < 0.05). The IPAQ scores of the NCs and patients with UA were significantly higher than in patients with STEMI and NSTEMI (P < 0.05). Notably higher HDS scores were recorded for the NCs compared to those of patients with UA, NSTEMI, and STEMI (P < 0.05). Consistent with these findings, compared with the NCs, the lowest levels of Bmal1, Clock, Cry1, Per2 and Rev-erbα mRNAs were detected in patients with STEMI, followed by patients with NSTEMI and then patients with UA (P < 0.05). Furthermore, the levels of MMP2 and MMP9 mRNA were significantly higher in the patients with STEMI, NSTEMI, and UA than those in the NCs (P < 0.05). In addition, we found that the levels of MMP mRNA negatively correlated with the levels of clock genes mRNAs (P < 0.05, respectively).
Conclusions:
Based on our data, the circadian rhythms and clock genes are correlatively with the occurrence of ACS, and the expression levels of clock genes are negatively correlated with plaque stability in ACS patients.
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