Abstract
Coronary plaque rupture is the most common cause of acute coronary syndrome. However, the timely biomarker-based diagnosis of plaque rupture remains a major unmet clinical challenge. Balloon dilatation and stent implantation during percutaneous coronary intervention (PCI) could cause plaque injury and rupture. Here we aimed to assess the possibility of circulating microRNAs (miRNAs) as biomarkers of acute coronary plaque rupture by virtue of the natural model of PCI-induced plaque rupture. Stable coronary artery disease patients underwent PCI with single stent implantation were recruited and a three-phase approach was conducted in the present study: (i) profiling of plasma miRNAs in a group of patients before (0 h) and after balloon dilatation for 1 h (1 h vs. 0 h), (ii) replication of significant miRNAs in the second group of patients (1 h vs. 0 h), (iii) validation of a multi-miRNAs panel in the third group of patients (0.5 h, 1 h vs. 0 h). Out of 24 miRNAs selected for replication, 6 miRNAs remained significantly associated with plaque rupture. In the validation phase, combinations of miR-483-5p and miR-451a showed the highest area under the receiver-operating-characteristic curve (AUC) (0.982; CI: 0.907-0.999) in patients with plaque rupture for 0.5 h; combinations of miR-483-5p and miR-155-5p showed the highest AUC (0.898; CI: 0.790-0.962) after plaque rupture for 1 h. In conclusion, using a profiling-replication-validation model, we identified 3 miRNAs including miR-155-5p, miR-483-5p and miR-451a, which may be biomarkers for the early identification of plaque rupture.
Highlights
Coronary plaque rupture is the most common cause of acute coronary syndrome (ACS), including unstable angina (UA), acute myocardial infarction (AMI), and sudden death [1]
It has been reported that some cytokines, chemokines, growth-factors and enzyme in circulation may be biomarkers of unstable plaque [2], but there are still not definite biomarkers of ruptured plaque, which may be partially due to lacking an appropriate model of plaque www.impactjournals.com/oncotarget rupture
To determine the effect of plaque rupture on the levels of circulating miRNAs, we compared the levels of 754 miRNAs in plasma samples obtained from 10 patients before (0 h) and after balloon dilatation for 1 h (1 h)
Summary
Coronary plaque rupture is the most common cause of acute coronary syndrome (ACS), including unstable angina (UA), acute myocardial infarction (AMI), and sudden death [1]. The accurate identification of patients with ACS caused by plaque rupture may allow early and preventative treatment to avoid the occurrence of adverse cardiovascular events. Pathological studies have shown that balloon dilatation could lead to atherosclerotic plaque rupture both in patients underwent percutaneous coronary intervention (PCI) [3,4,5,6,7] and in animal models of atherosclerosis [8, 9]. PCI-induced plaque injury could be used to mimic plaque rupture that occurred in patients with coronary artery disease (CAD). Patients underwent PCI may be the natural model to study the biomarkers of plaque rupture
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