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异常的昼夜节律与急性冠脉综合征患者的斑块不稳定有关。

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

作者信息

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

机构信息

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

Institute of Cardiovascular Diseases, China Three Gorges University Yichang 443000, Hubei Province, PR China.

出版信息

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

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) (). The IPAQ scores of the NCs and patients with UA were significantly higher than in patients with STEMI and NSTEMI (). Notably higher HDS scores were recorded for the NCs compared to those of patients with UA, NSTEMI, and STEMI (). 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 (). Furthermore, the levels of MMP2 and MMP9 mRNA were significantly higher in the patients with STEMI, NSTEMI, and UA than those in the NCs (). In addition, we found that the levels of MMP mRNA negatively correlated with the levels of clock genes mRNAs (, 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.

摘要

目的

急性冠状动脉综合征(ACS)是全球发病和死亡的主要原因之一,是最严重的心血管疾病之一。昼夜节律几乎存在于所有生物体中。在临床实践中,我们发现ACS与这些昼夜节律密切相关。然而,昼夜节律与ACS患者斑块不稳定性之间的关系尚未完全明确。本研究的目的是为昼夜节律与ACS患者斑块不稳定性之间的关系提供新的见解。

方法

本研究纳入了ACS患者和冠状动脉功能正常的个体。使用雅典失眠量表(AIS)、匹兹堡睡眠质量指数(PSQI)、国际体力活动问卷(IPAQ)和健康饮食评分(HDS)来评估昼夜节律。此外,采用定量实时聚合酶链反应(qRT-PCR)评估肌肉芳香烃受体核转运体样蛋白1(Bmal1)、昼夜运动输出周期蛋白(Clock)、隐花色素1(Cry1)、周期蛋白2(Per2)、核受体亚家族1 D组成员1(Rev-erbα)以及基质金属蛋白酶MMP2和MMP9的mRNA表达水平。

结果

ST段抬高型心肌梗死(STEMI)、非ST段抬高型心肌梗死(NSTEMI)和不稳定型心绞痛(UA)患者的AIS评分和PSQI评分显著高于正常对照组(NCs)()。NCs和UA患者的IPAQ评分显著高于STEMI和NSTEMI患者()。值得注意的是,NCs的HDS评分明显高于UA、NSTEMI和STEMI患者()。与这些结果一致,与NCs相比,STEMI患者中Bmal1、Clock、Cry1、Per2和Rev-erbα mRNA的水平最低,其次是NSTEMI患者,然后是UA患者()。此外,STEMI、NSTEMI和UA患者的MMP2和MMP9 mRNA水平显著高于NCs()。此外,我们发现MMP mRNA水平与时钟基因mRNA水平呈负相关(,分别)。

结论

基于我们的数据,昼夜节律和时钟基因与ACS的发生相关,并且时钟基因的表达水平与ACS患者的斑块稳定性呈负相关。

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