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Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
Circulating MicroRNAs Characterizing Patients with Insufficient Coronary Collateral Artery Function
Nazanin Hakimzadeh1, A Yaël Nossent2, Anja M van der Laan3
1Department of Biomedical Engineering & Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Background:
Coronary collateral arteries function as natural bypasses in the event of coronary obstruction. The degree of collateral network development significantly impacts the outcome of patients after an acute myocardial infarction (AMI). MicroRNAs (miRNAs, miRs) have arisen as biomarkers to identify heterogeneous patients, as well as new therapeutic targets in cardiovascular disease. We sought to identify miRNAs that are differentially expressed in chronic total occlusion (CTO) patients with well or poorly developed collateral arteries.
Methods And Results:
Forty-one CTO patients undergoing coronary angiography and invasive assessment of their coronary collateralization were dichotomized based on their collateral flow index (CFI). After miRNA profiling was conducted on aortic plasma, four miRNAs were selected for validation by real-time quantitative reverse transcription polymerase chain reaction in patients with low (CFI<0.39) and high (CFI>0.39) collateral artery capacity. We confirmed significantly elevated levels of miR423-5p (p<0.05), miR10b (p<0.05), miR30d (p<0.05) and miR126 (p<0.001) in patients with insufficient collateral network development. We further demonstrated that each of these miRNAs could serve as circulating biomarkers to discriminate patients with low collateral capacity (p<0.01 for each miRNA). We also determined significantly greater expression of miR30d (p<0.05) and miR126 (p<0.001) in CTO patients relative to healthy controls.
Conclusion:
The present study identifies differentially expressed miRNAs in patients with high versus low coronary collateral capacity. We have shown that these miRNAs can function as circulating biomarkers to discriminate between patients with insufficient or sufficient collateralization. This is the first study to identify miRNAs linked to coronary collateral vessel function in humans.
Insights
MicroRNAs (miRNAs) in blood can identify patients with poor coronary collateral artery development. Elevated levels of miR423-5p, miR10b, miR30d, and miR126 indicate insufficient collateral capacity in chronic total occlusion patients.
Area of Science:
- Cardiovascular Biology
- Molecular Diagnostics
- Biomarker Discovery
Background:
- Coronary collateral arteries act as natural bypasses during coronary obstruction.
- Collateral network development is crucial for patient outcomes after acute myocardial infarction (AMI).
- MicroRNAs (miRNAs) are emerging as biomarkers and therapeutic targets in cardiovascular disease.
Purpose of the Study:
- To identify differentially expressed miRNAs in chronic total occlusion (CTO) patients with varying degrees of coronary collateral artery development.
- To assess the potential of identified miRNAs as circulating biomarkers for collateral capacity.
Main Methods:
- Coronary angiography and collateral flow index (CFI) assessment in 41 CTO patients.
- miRNA profiling of aortic plasma followed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) validation.
- Dichotomization of patients into low (CFI<0.39) and high (CFI>0.39) collateral capacity groups.
Main Results:
- Four miRNAs (miR423-5p, miR10b, miR30d, miR126) were significantly elevated in patients with insufficient collateral network development (low CFI).
- These four miRNAs demonstrated utility as circulating biomarkers to discriminate between patients with low and high collateral capacity.
- miR30d and miR126 showed significantly greater expression in CTO patients compared to healthy controls.
Conclusions:
- This study identifies specific miRNAs associated with coronary collateral capacity in CTO patients.
- The identified miRNAs can serve as non-invasive biomarkers to assess collateral function.
- This research is the first to link specific miRNAs to coronary collateral vessel function in humans.
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