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Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
Predicted Value of MicroRNAs, Vascular Endothelial Growth Factor, and Intermediate Monocytes in the Left Adverse
Raquel Del Toro1,2, Isabel Galeano-Otero1,2, Elisa Bevilacqua2
1Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Seville, Spain.
Insights
Pro-inflammatory intermediate monocytes, vascular endothelial growth factor (VEGF), and specific microRNAs (miRNAs) measured after primary percutaneous coronary intervention (PPCI) can predict left ventricular adverse remodeling (LVAR) in ST-segment elevation myocardial infarction (STEMI) patients.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Background:
- Primary percutaneous coronary intervention (PPCI) improves survival in ST-segment elevation myocardial infarction (STEMI) but does not prevent left ventricular adverse remodeling (LVAR).
- Identifying biomarkers for LVAR post-PPCI is crucial for patient management and improving long-term outcomes.
Purpose of the Study:
- To investigate pro-inflammatory cell populations, cytokines, and microRNAs (miRNAs) as prognostic biomarkers for LVAR after PPCI in STEMI patients.
- To characterize the role of specific immune cells and molecular factors in predicting adverse cardiac remodeling.
Main Methods:
- Flow cytometry to assess pro-inflammatory monocyte subsets (classical, intermediate) before and after PPCI.
- miRNA microarray and multiplex ELISA to analyze miRNA expression and cytokine levels (including VEGF) in patient serum and peripheral blood mononuclear cells (PBMCs).
Main Results:
- Increased levels of intermediate monocytes and vascular endothelial growth factor (VEGF) were observed 6 hours post-PPCI in patients who later developed LVAR.
- Differential expression of specific miRNAs (miR-16, miR-21-5p, miR-29a-3p) was confirmed in LVAR patients.
- Combined analysis of intermediate monocytes, VEGF, and miRNAs demonstrated high accuracy in predicting LVAR development.
Conclusions:
- Intermediate monocytes, VEGF, and specific miRNAs are promising biomarkers for predicting LVAR in STEMI patients post-PPCI.
- Combined biomarker analysis offers a robust strategy for identifying patients at high risk of adverse cardiac remodeling.
Background:
Primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI) improves the survival of patients; nevertheless, some patients develop left ventricular adverse remodeling (LVAR) a few months after the intervention. The main objective of this study was to characterize the role of pro-inflammatory cell populations, related cytokines, and microRNAs (miRNAs) released after PPCI as reliable prognostic biomarkers for LVAR in patients with STEMI.
Methods:
We evaluated the level of pro-inflammatory subsets, before and after revascularization, 1 and 6 months after PPCI, using flow cytometry. We also performed a miRNA microarray in isolated peripheral blood mononuclear cells (PBMCs) and examined the levels of 27 cytokines in patients' serum of patients by multiplex ELISA.
Results:
We observed that the levels of classical and intermediate monocytes increased 6 h after PPCI in patients who developed LVAR later. Multivariate regression analysis and ROC curves indicated that intermediate monocytes, after PPCI, were the best monocyte subset that correlated with LVAR. Within the 27 evaluated cytokines evaluated, we found that the increase in the level of vascular endothelial growth factor (VEGF) correlated with LVAR. Furthermore, the microarray analysis of PBMCs determined that up to 1,209 miRNAs were differentially expressed 6 h after PPCI in LVAR patients, compared with those who did not develop LVAR. Using RT-qPCR we confirmed a significant increase in miR-16, miR-21-5p, and miR-29a-3p, suggested to modulate the expression of different cytokines, 6 h post-PPCI in LVAR patients. Interestingly, we determined that the combined analysis of the levels of the intermediate monocyte subpopulation, VEGF, and miRNAs gave a better association with LVAR appearance. Similarly, combined ROC analysis provided high accurate specificity and sensibility to identify STEMI patients who will develop LVAR.
Conclusion:
Our data suggest that the combined analysis of intermediate monocytes, VEGF, and miRNAs predicts LVAR in STEMI patients.
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