miR-941 as a promising biomarker for acute coronary syndrome

Abstract

Background: 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).

Methods: 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).

Results: 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.

Conclusion: miR-941 expression was relatively higher in patients with ACS and STEMI. Thus, miR-941 may be a potential biomarker of ACS or STEMI.

Keywords: Acute ST-segment elevation myocardial infarction; Acute coronary artery disease; Stable angina; microRNA.

Fig. 1

Schematic of the study design

Fig. 2

Gene ontology (GO) analysis

Fig. 3

Pathway analysis

Fig. 4

Microarray pathway network. The red rectangles are miRNAs, the purple circle are pathways, and the green lines represented the regulatory connections between miRNAs and pathways

Fig. 5

Expression profiles of candidate miRNAs in patients with and without CAD. The three candidate miRNAs were evaluated with qRT-PCR using 72 samples, including 16 non-CAD, 20 SA, 18 NSTE-ACS, and 18 STEMI samples. miR-941 was significantly upregulated in the SA, NSTE-ACS, and STEMI groups compared with that in non-CAD patients (a). miR-182-5p (b) and miR-363-3p (c) were not significantly different in patients with CAD (SA, NSTE-ACS, and STEMI) compared with that in patients without CAD. Abbreviations: CAD: coronary artery disease, SA: stable angina, NSTE-ACS: non-ST elevation acute coronary syndromes, STEMI: ST elevation myocardial infarction. *P < 0.05, ^Δ P < 0.001

Fig. 6

Expression profiles of candidate miRNAs in patients with SA, NSTE-ACS, and STEMI. The three candidate miRNAs were evaluated by qRT-PCR using 56 samples (20 cases of SA, 18 cases of NSTE-ACS, and 18 cases of STEMI). (a) miR-941, (b) miR-182-5p, and (c) miR-363-3p are shown. Abbreviations: CAD, coronary artery disease; SA, stable angina; NSTE-ACS, non-ST elevation acute coronary syndrome; STEMI, ST elevation myocardial infarction. *P < 0.05, ^Δ P < 0.001

Fig. 7

Expression profiles of miR-941 in patients with and without ACS. miR-941 expression was evaluated by qRT-PCR using 72 samples (36 patients without ACS and 36 patients with ACS). Abbreviations: ACS, acute coronary syndrome. ^Δ P < 0.01

Fig. 8

ROC curve analysis. a Expression profiles of miR-941 in patients with STEMI and without CAD. b Expression profiles of miR-941 in patients with STEMI and SA. c Expression profiles of miR-941 in patients with STEMI and NSTE-ACS. d Expression profiles of miR-941 in patients with and without ACS