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MiR-423 is differentially expressed in patients with stable and unstable coronary artery disease: A pilot study
Barbara Rizzacasa1, Elena Morini1, Ruggiero Mango2
1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
Insights
MicroRNA miR-423-5p shows altered expression in patients with coronary artery disease (CAD). Its levels in plasma and blood cells may serve as a novel biomarker for risk stratification in CAD patients.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Biomarker Discovery
Background:
- Coronary artery disease (CAD) and acute myocardial infarction (AMI) are leading global causes of mortality.
- Identifying unique factors predisposing to AMI in CAD patients is crucial for risk stratification.
- Circulating microRNAs (miRNAs) show potential as diagnostic biomarkers for cardiac injuries and risk assessment.
Purpose of the Study:
- To investigate differential microRNA expression in patients with stable CAD versus those experiencing AMI.
- To identify specific microRNAs that can serve as biomarkers for distinguishing between stable CAD and acute myocardial infarction.
- To evaluate the potential of miR-423-5p as a biomarker for risk stratification in CAD patients over time.
Main Methods:
- An array-based approach was used to analyze the expression of 84 circulating miRNAs in plasma from stable CAD and AMI patients.
- miR-423-5p expression was further validated in a larger cohort and in peripheral blood mononuclear cells (PBMCs).
- Receiver operating characteristic (ROC) analyses were performed to assess the discriminatory power of miR-423-5p.
Main Results:
- 27 miRNAs were found to be differentially expressed between stable CAD and AMI patients.
- Circulating miR-423-5p was significantly down-regulated within 24 hours of AMI and up-regulated 6 months post-AMI.
- Plasma miR-423-5p distinguished stable from unstable CAD (AUC = 0.7143).
- Blood cell miR-423-5p showed higher discriminatory power, differentiating acute AMI from post-AMI states (AUC = 0.8529) and stable CAD from post-AMI patients (AUC = 0.7355).
Conclusions:
- miR-423-5p expression levels in both plasma and blood cells show promise as novel biomarkers.
- These findings suggest miR-423-5p could aid in the risk stratification of coronary artery disease patients.
- Further research is warranted to validate miR-423-5p for clinical application in cardiovascular risk assessment.
Abstract:
Coronary artery disease (CAD) and acute myocardial infarction (AMI) are the leading causes of death worldwide. Since only a subset of CAD patients develops myocardial infarction, it is likely that unique factors predispose to AMI. Circulating microRNAs represent diagnostic powerful biomarkers for detection of heart injuries and patients' risk stratification. Using an array-based approach, the expression of 84 circulating miRNAs was analyzed in plasma of pooled stable CAD patients (CAD; n = 5) and unstable CAD patients (AMI_T0; n = 5) enrolled within 24 hours from an AMI event. The array experiments showed 27 miRNAs differentially expressed with a two-fold up- or down-regulation (10 up- and 17 down-regulated miRNAs). Among them, miR-423-5p dis-regulation was confirmed in a larger case study (n = 99). Circulating miR-423-5p resulted to be significantly down-regulated within 24 hours from the AMI event (FC = -2, p≤0.05). Interestingly, miR-423-5p expression resulted to be increased (FC = +2; p≤0.005) in a subgroup of the same AMI patients (AMI_T1; n = 11) analyzed after 6 months from the acute event. We extended miR-423-5p expression study on PBMCs (peripheral blood mononuclear cells), confirming also in this tissue its up-regulation at 6 months post-AMI. Receiver operating characteristic analyses (ROC) were performed to detect the power of miR-423-5p to discriminate stable and unstable CAD. In plasma, miR-423-5p expression accurately distinguishes stable and unstable CAD patients (AUC = 0.7143, p≤0.005). Interestingly, the highest discriminatory value (AUC = 0.8529 p≤0.0005) was identified in blood cells, where miR-423-5p expression is able to differentiate unstable CAD patients during an acute event (AMI_T0) from those at six months post-AMI (AMI_T1). Furthermore, cellular miR-423-5p may discriminate also stable CAD patients from unstable CAD patients after six months post-AMI (AUC = 0.7355 p≤0.05). The results of this pilot-study suggest that miR-423-5p expression level both in plasma and blood cells, could represent a new promising biomarker for risk stratification of CAD patients.
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