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Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
MicroRNA sequencing in patients with coronary artery disease - considerations for use as biomarker for thrombotic
Chimnonso P Onuoha1, Joseph Ipe1, Edward Simpson2
1Department of Medicine/Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Insights
Circulating microRNAs (miRNAs) in whole blood show potential as biomarkers for predicting recurrent myocardial infarction (MI) after coronary artery disease (CAD) interventions. Whole blood analysis may be superior to plasma for identifying patients at risk.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Medicine
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression.
- Circulating miRNAs are being investigated as potential biomarkers for cardiovascular diseases.
- Identifying patients with coronary artery disease (CAD) at risk for recurrent myocardial infarction (MI) after percutaneous coronary interventions (PCIs) is crucial for secondary prevention.
Purpose of the Study:
- To investigate the potential of circulating miRNA levels in whole blood and plasma to identify patients with CAD at risk for recurrent MI after PCI.
- To compare the utility of whole blood versus plasma samples for miRNA profiling in this patient population.
Main Methods:
- Subjects with CAD were selected from the GENCATH cardiac catheterization biobank.
- Next-generation miRNA sequencing was performed on plasma and whole blood samples.
- Patients with recurrent MI post-PCI were compared to those without recurrent MI in initial and replication cohorts.
Main Results:
- 164 miRNAs from whole blood were differentially expressed in the replication cohort (p < 0.05), with 69 significant after FDR correction.
- No significant differences in plasma miRNAs were observed between groups after FDR correction.
- Correlation between plasma and whole blood miRNA assays was variable; only two miRNAs were concordant and significant in both.
Conclusions:
- MiRNA profiling, particularly using whole blood, shows promise as a future biomarker for disease prognosis and treatment response in secondary prevention for CAD patients post-PCI.
- Whole blood appears to be a more suitable sample source than plasma for identifying risk of recurrent MI.
Abstract:
MicroRNAs (miRNAs) are small RNAs integral in the regulation of gene expression. Analysis of circulating miRNA levels may identify patients with coronary artery disease (CAD) at risk for recurrent myocardial infarction (MI) after percutaneous coronary interventions (PCIs). Subjects with CAD were selected from the GENCATH cardiac catheterization biobank. Subjects with recurrent MI after PCI were compared with those without recurrent MI during follow-up in the initial (n = 48) and replication cohort (n = 67). Next generation MiRNA sequencing was performed on plasma samples and whole blood samples fixed with PAXGENE tubes upon collection. Overall, 164 miRNAs derived from whole blood were differentially expressed in the replication cohort between subjects with and without recurrent MI events (p < 0.05), with 69 remaining significant after false-discovery rate (FDR) correction. None of the miRNAs in plasma was significantly different by FDR among subjects with and without MI. Overall, correlation between direction of effects between plasma and whole blood assays was variable, and only two miRNAs were concordant and significant in both. Associations of miRNA with vascular disease, MI, and thrombosis were further explored. MiRNA profiling has potential as the future biomarker for disease prognosis and treatment response marker in secondary treatment of patients with CAD after PCI. Whole blood may be the preferred sample source as compared to plasma.
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