RNA-seq identifies circulating miRNAs as potential biomarkers for plaque rupture in patients with ST-segment elevation myocardial infarction

Background: Plaque rupture (PR) and plaque erosion (PE) are the two major pathological phenotypes in acute coronary syndrome. Since microRNAs have been found to be involved in the mechanisms of PR and PE, we investigated the diagnostic utility of microRNAs in differentiating between patients with PR and patients with PE. Methods: MicroRNA sequencing was performed on plasma from 21 patients with PR, 20 patients with PE and 17 healthy control subjects (HCs). 24 miRNAs were selected for validation in 20 PR patients and 20 PE patients and 8 miRNAs were further validated in an independent replication cohort (82 patients with PR, 84 patients with PE and 59 HCs) by applying quantitative real-time polymerase chain reaction. Then we analyzed pathways associated with significant miRNAs in PR. Results: MiR-744-3p, miR-324-3p and miR-330-3p were significantly upregulated in the PR group compared with the PE group (Log(10)miR-744-3p: 0.26[-0.28-1.57] versus0.41[0.83-0.03], p(adj) < 0.001; Log(10)miR-3243p: 0.40[0.09-0.84] versus0.12[0.53-0.29], p(adj) < 0.001; Log(10)miR-330-3p: 0.34[0.08-0.93] versus0.07[0.65-0.22], p(adj) < 0.001), The area under the receiver operating characteristic curve for the combination of these three miRNAs in distinguishing between PR from PE in training and test set was 0.764 (0.679-0.850, sensitivity = 86.2%, specificity = 54.4%, P < 0.001) and 0.768 (0.637-0.898, sensitivity,65.4%, specificity:80.0%, P = 0.001), respectively. Conclusion: A set of circulating microRNAs (miR-744-3p, miR-330-3p, and miR-324-3p) is associated with PR and has clinical utility as a diagnostic marker for distinguishing the plaque phenotype in STEMI patients.

Automated summary

The study identified that miR-744-3p, miR-324-3p, and miR-330-3p were significantly upregulated in patients with plaque rupture (PR) compared to those with plaque erosion (PE). The combination of these three miRNAs had clinical utility in distinguishing between PR and PE, with an area under the receiver operating characteristic curve of 0.764 and 0.768 in training and test sets, respectively. These circulating microRNAs could serve as diagnostic markers for distinguishing plaque phenotype in ST-elevation myocardial infarction patients.