Abnormal circadian rhythms are associated with plaque instability in acute coronary syndrome patients

Zai-Qiang Zhang; Jia-Wang Ding; Xin-An Wang; Cai-Yun Luo; Bin Yu; Xia-Xia Zheng; Tian Zhou; Bai-Xue Shang; Xiao-Hong Tong; Jing Zhang

Abnormal circadian rhythms are associated with plaque instability in acute coronary syndrome patients

Int J Clin Exp Pathol. 2019 Oct 1;12(10):3761-3771. eCollection 2019.

Authors

Zai-Qiang Zhang^{1

2}, Jia-Wang Ding^{1

2}, Xin-An Wang^{1

2}, Cai-Yun Luo^{1

2}, Bin Yu^{1

2}, Xia-Xia Zheng^{1

2}, Tian Zhou^{1

2}, Bai-Xue Shang^{1

2}, Xiao-Hong Tong^{1

2}, Jing Zhang^{1

2}

Affiliations

¹ Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University Yichang 443000, Hubei Province, PR China.
² Institute of Cardiovascular Diseases, China Three Gorges University Yichang 443000, Hubei Province, PR China.

PMID: 31933764
PMCID: PMC6949736

Abstract

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.

Keywords: Acute coronary syndrome (ACS); circadian rhythms; plaque stability.