Abstract
Transcriptome analysis constitutes one of the major methods of elucidation of the genetic basis underlying the pathogenesis of various diseases. The post-transcriptional regulation of gene expression is mainly provided by microRNAs. Their remarkable stability in biological fluids and their high sensitivity to disease alteration indicates their potential role as biomarkers. Given the high mortality and morbidity of cardiovascular diseases, novel predictive biomarkers are sorely needed. Our study focuses for the first time on assessing potential biomarkers of acute coronary syndrome (ACS) based on the microRNA profiles of platelets. The study showed the overexpression of eight platelet microRNAs in ACS (miR-142-3p; miR-107; miR-338-3p, miR-223-3p, miR-21-5p, miR-130b-3p, miR-301a-3p, miR-221-3p) associated with platelet reactivity and functionality. Our results show that the combined model based on miR-142-3p and aspartate transaminase reached 82% sensitivity and 88% specificity in the differentiation of the studied groups. Furthermore, the analyzed miRNAs were shown to cluster into two orthogonal groups, regulated by two different biological factors. Bioinformatic analysis demonstrated that one group of microRNAs may be associated with the physiological processes of platelets, whereas the other group may be linked to platelet–vascular environment interactions. This analysis paves the way towards a better understanding of the role of platelet microRNAs in ACS pathophysiology and better modeling of the risk of ACS.
Highlights
Our study showed that of the selected miRNAs, miR-142-3p is one of the most overexpressed in acute coronary syndrome (ACS) patients compared to healthy controls (FC = 5.16 (95%CI: 2.59–10.28); p < 0.0001), both in microarray and RT-qPCR analysis
Our results showed that mRNAs targeted by miRNAs included in cluster 1, capable of differentiating ACS patients from healthy donors, presented a seven-fold higher number of transcripts for genes associated with the positive regulation of GTPase activity and positive regulation of PLC activity, over a six-fold elevated number of genes linked with the response to hypoxia, a nearly five-fold higher number of genes related to the regulation of chemotaxis and signaling of phosphatidylinositol 3-kinase, and a more than two-times increased number of genes associated with signal transduction, response to drugs, and the regulation of nitric oxide biosynthesis
The results of our study showed a significantly increased expression of miR-142-3p; miR-107; miR-338-3p, miR-223-3p, miR-21-5p, miR-130b-3p, miR-301a-3p, and miR-221-3p in the group of ACS patients compared to healthy volunteers
Summary
Epidemiological studies have demonstrated that 85% of all deaths caused by CVDs were associated with stroke and acute coronary syndrome (ACS) [1]. In the early assessment of symptom presentation, 12-lead electrocardiography and the cardiac troponin level are still considered the gold standard in diagnosis and constitute a strong foundation in the ACS triage [2,3]. ACS biomarkers in current clinical usage are focused on the diagnosis of patients during ischemic events, enabling monitoring of the dynamics of myocardial ischemia [2]. There are no biomarkers that can be used to evaluate the potential risk of ACS development before ischemia occurs. The establishment of prognostic biomarkers would enable the implementation of preventive treatment, reducing the risk of ACS
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