Bai Ruina, Yang Qiaoning, Xi Ruixi, Li Lizhi, Shi Dazhuo, Chen Keji
Xiyuan Hospital, China Academy of Chinese Medical Sciences, 1 Xiyuan Caochang, Haidian district, Beijing, China.
BMC Cardiovasc Disord. 2017 Aug 22;17(1):227. doi: 10.1186/s12872-017-0653-8.
Circulating miRNAs can function as biomarkers for diagnosis, treatment, and prevention of diseases. However, it is unclear whether miRNAs can be used as biomarkers for acute coronary syndrome (ACS). To this end, we applied gene chip technology to analyze miRNA expression in patients with stable angina (SA), non-ST elevation ACS (NSTE-ACS), and ST-segment elevation myocardial infarction (STEMI).
We enrolled patients with chest pain who underwent diagnostic coronary angiography, including five patients each with SA, NSTE-ACS, or STEMI, and five controls without coronary artery disease (CAD) but with three or more risk factors. After microarray analysis, differential miRNA expression was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR).
Compared with those in patients with STEMI, differentially expressed microRNAs in controls and patients with SA or NSTE-ACS were involved in inflammation, protein phosphorylation, and cell adhesion. Pathway analysis showed that differentially expressed miRNAs were related to the mitogen-activated protein kinase signaling, calcium ion pathways, and cell adhesion pathways. Compared with their expression levels in patients with STEMI, miR-941, miR-363-3p, and miR-182-5p were significantly up-regulated (fold-change: 2.0 or more, P < 0.05) in controls and patients with SA or NSTE-ACS. Further, qRT-PCR showed that plasma miR-941 level was elevated in patients with NSTE-ACS or STEMI as compared with that in patients without CAD (fold-change: 1.65 and 2.28, respectively; P < 0.05). Additionally, miR-941 expression was significantly elevated in the STEMI group compared with that in the SA (P < 0.01) and NSTE-ACS groups (P < 0.05). Similarly, miR-941 expression was higher in patients with ACS (NSTE-ACS or STEMI) than in patients without ACS (without CAD or with SA; P < 0.01). There were no significant differences in miR-182-5p and miR-363-3p expression. The areas under the receiver operating characteristic curves were 0.896, 0.808, and 0.781 for patients in the control, SA, and NSTE-ACS groups, respectively, compared with that for patients with STEMI; that for the ACS group compared with the non-ACS group was 0.734.
miR-941 expression was relatively higher in patients with ACS and STEMI. Thus, miR-941 may be a potential biomarker of ACS or STEMI.
循环微小RNA(miRNA)可作为疾病诊断、治疗和预防的生物标志物。然而,miRNA是否可作为急性冠状动脉综合征(ACS)的生物标志物尚不清楚。为此,我们应用基因芯片技术分析稳定型心绞痛(SA)、非ST段抬高型ACS(NSTE-ACS)和ST段抬高型心肌梗死(STEMI)患者的miRNA表达。
我们纳入了因胸痛接受诊断性冠状动脉造影的患者,包括SA、NSTE-ACS或STEMI患者各5例,以及5例无冠状动脉疾病(CAD)但有3个或更多危险因素的对照。经过微阵列分析后,通过定量实时逆转录聚合酶链反应(qRT-PCR)确认差异miRNA表达。
与STEMI患者相比,对照以及SA或NSTE-ACS患者中差异表达的微小RNA参与了炎症、蛋白质磷酸化和细胞黏附过程。通路分析表明,差异表达的miRNA与丝裂原活化蛋白激酶信号传导、钙离子通路和细胞黏附通路有关。与它们在STEMI患者中的表达水平相比,对照以及SA或NSTE-ACS患者中的miR-941、miR-363-3p和miR-182-5p显著上调(倍数变化:2.0或更高,P < 0.05)。此外,qRT-PCR显示,与无CAD患者相比,NSTE-ACS或STEMI患者的血浆miR-941水平升高(倍数变化分别为1.65和2.28;P < 0.05)。此外,与SA组(P < 0.01)和NSTE-ACS组(P < 0.05)相比,STEMI组中miR-941表达显著升高。同样,ACS(NSTE-ACS或STEMI)患者的miR-941表达高于无ACS患者(无CAD或有SA;P < 0.01)。miR-182-5p和miR-3